Publications by authors named "Rodolfo Campos"

82 Publications

Phylogeography and evolutionary history of hepatitis E virus genotype 3 in Argentina.

Trans R Soc Trop Med Hyg 2021 Mar 19. Epub 2021 Mar 19.

Instituto de Virología 'Dr J. M. Vanella', Facultad de Ciencias Médicas, Universidad Nacional de Córdoba. Enfermera Gordillo Gómez s/n. CP: 5016. Córdoba, Argentina.

Background: Few studies about the evolutionary history of the hepatitis E virus (HEV) have been conducted. The aim of our work was to investigate and make inferences about the origin and routes of dispersion of HEV-3 in Argentina.

Methods: Phylogenetic, coalescent and phylogeographic analyses were performed using a 322-bp ORF2 genomic fragment of all HEV-3 sequences with known date and place of isolation published at GenBank until May 2018 (n=926), including 16 Argentinian sequences (isolated from pigs, water and humans).

Results: Phylogenetic analysis revealed two clades within HEV-3: abchij and efg. All Argentinian samples were grouped intermingled within clade 3abchij. The coalescent analysis showed that the most recent common ancestor for the clade 3abchij would have existed around the year 1967 (95% highest posterior density (HPD): 1963-1970). The estimated substitution rate was 1.01×10-2 (95%HPD: 9.3×10-3-1.09×10-2) substitutions/site/y, comparable with the rate previously described. The phylogeographic approach revealed a correspondence between phylogeny and place of origin for Argentinian samples, suggesting many HEV introductions in the country, probably from Europe and Japan.

Conclusions: This is the first evolutionary inference of HEV-3 that includes Argentinian strains, showing the circulation of many HEV-3 subtypes, obtained from different sources and places, with recent diversification processes.

Accession Numbers: [KX812460], [KX812461], [KX812462], [KX812465], [KX812466], [KX812467], [KX812468], [KX812469].
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http://dx.doi.org/10.1093/trstmh/trab044DOI Listing
March 2021

Genotypes and phylogenetic analysis of adenovirus in children with respiratory infection in Buenos Aires, Argentina (2000-2018).

PLoS One 2021 8;16(3):e0248191. Epub 2021 Mar 8.

Unidad de Virología, Centro de Educación Médica e Investigaciones Clínicas (CEMIC) Hospital Universitario, Ciudad de Buenos Aires, Argentina.

Human adenoviruses (HAdV) are one of the most frequent causes of respiratory infections around the world, causing mild to severe disease. In Argentina, many studies focused on the association of HAdV respiratory infection with severe disease and fatal outcomes leading to the discovery in 1984 of a genomic variant 7h associated with high fatality. Although several molecular studies reported the presence of at least 4 HAdV species (B, C, D and E) in Argentina, few sequences were available in the databases. In this study, sequences from the hexon gene region were obtained from 141 patients as a first approach to assess the genetic diversity of HAdVs circulating in Buenos Aires, Argentina. Phylogenetic analysis of these sequences and others recovered from public databases confirmed the circulation of the four above-mentioned species represented by 11 genotypes, with predominance in species B and C and shifts in their proportion in the studied period (2000 to 2018). The variants detected in Argentina, for most of the genotypes, were similar to those already described in other countries. However, uncommon lineages belonging to genotypes C2, C5 and E4 were detected, which might indicate the circulation of local variants and will deserve further studies of whole-genome sequences.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248191PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939361PMC
March 2021

Long-term evolution of hepatitis B virus genotype F: Strong association between viral diversification and the prehistoric settlement of Central and South America.

J Viral Hepat 2020 06 28;27(6):620-630. Epub 2020 Feb 28.

Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Universidad de Buenos Aires, Buenos Aires, Argentina.

The genotype F (HBV-F) is an autochthonous Native American strain of the hepatitis B virus. In this study, we reconstruct the HBV-F long-term evolution under a hypothesis of co-divergence with humans in Central and South America, since their entry into the region 14.5-16 thousand years ago. The Bayesian phylogeographic reconstruction supported a virus-host co-expansion; however, two evolutionary scenarios would have been present. Whereas subgenotype F1 spreads along a Pacific coastal route and would have evolved associated with Central American and Andean cultures from the west of the continent, subgenotypes F2-F6 spread along the Atlantic coastline and inner pathways associated with communities inhabiting the tropical forest lowlands. Then, we propose a model for HBV-F evolution in which the selection of differential biological characteristics in these two main groups would be related to their evolution in host populations with different genetic backgrounds and dissimilar demographic conditions.
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http://dx.doi.org/10.1111/jvh.13273DOI Listing
June 2020

Genetic diversity of the JC polyomavirus (JCPyV) and mitochondrial DNA ancestry in Misiones, Argentina.

Infect Genet Evol 2019 11 22;75:104011. Epub 2019 Aug 22.

Laboratorio de Biología Molecular Aplicada, Universidad Nacional de Misiones, Posadas, Misiones, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.

Background: The use of human and viral genetic markers offers a novel way to study human migration in multiethnic populations of Latin America.

Objectives: Our goal was to characterize the genetic diversity and geographical origins of JC Polyomavirus (JCPyV) and the genetic ancestry of mitochondrial DNA (mtDNA) in inhabitants from 25 de Mayo, Misiones-Argentina, a small village of largely German ancestry located close to the border with Brazil. We also evaluated the extent of agreement between viral and mtDNA markers for the different ancestry components of this population.

Study Design: 68 individuals were analyzed for JCPyV and mtDNA diversity. JCPyV detection and typing was conducted in urine samples by PCR amplification, sequencing and phylogenetic analysis of the VP1 gene. mtDNA ancestry was assessed through HVS1 sequencing, with the resulting haplotypes being classified into haplogroups of Amerindian, European and African origin. The distribution of JCPyV diversity and mtDNA ancestry in the population was statistically evaluated by Fisher exact test and the level of agreement of both markers at the individual level was evaluated by Cohen's kappa coefficient.

Results: Our analysis showed that 57.4% of the samples were positive for JCPyV. Of these, the 47.6% were Asian-American Type 2, 33.3% European Type 1 and 19.1% African Type 3 in origin. The mtDNA ancestry of the study participants was 33.3% Amerindian and 66.7% European. There was a significant difference among the distribution of JCPyV diversity and mtDNA ancestry (p = 0.009) and at the individual level there was no correlation between the distribution of the both markers (κ = 0.154, p = 0.297).

Conclusion: The apparent incongruence between JCPyV diversity and mtDNA ancestry may reflect the original settlement process and more recent migration to 25 de Mayo, the latter involving viral spread through migrants from Brazil. Some potential limitations to our interpretations are also discussed.
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http://dx.doi.org/10.1016/j.meegid.2019.104011DOI Listing
November 2019

Hepatitis B Virus X Gene Differentially Modulates Subgenotype F1b and F4 Replication.

Viruses 2019 07 18;11(7). Epub 2019 Jul 18.

Cátedra de Virología, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires 1113, Argentina.

Hepatitis B virus (HBV) is classified into ten genotypes and numerous subgenotypes (sgt). In particular, sgt F1b and sgt F4, native of Latin America, have been associated with differences in clinical and virological characteristics. Hepatitis B virus X protein (HBx) is a multifunctional regulatory protein associated with the modulation of viral transcription and replication. In this work, we analyzed the role of the X gene and the encoded X protein in sgtF1b and sgtF4 replication. Transfection with HBx deficient genomes revealed remarkable differences in the replicative capacity of sgtF1b and sgtF4 mutants. The silencing of HBx increased sgtF1b X(-) transcription and replication by more than 2.5 fold compared to the wild type variant, while it decreased sgtF4 X(-) transcription and replication by more than 3 fold. Trans-complementation of HBx restore sgtF1b and sgtF4 wild type transcription and replication levels. In addition, transfection with chimeric variants, carrying wild type (F1b/XF4 and F4/XF1b) or mutated (F1b/X(-)F4 and F4/X(-)F1b) X gene of one sgt in the backbone of the other sgt, showed that the nucleotide sequence of the X gene, that includes regulatory elements that modulate pgRNA transcription, was responsible for the disparity observed between sgtF1b X(-) and sgtF4 X(-). These results showed that sgtF1b and sgtF4 X gene play a central role in regulating HBV transcription and replication, which eventually lead to a common purpose, to reach wild type replication levels of sgtF1b and sgtF4 viruses.
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http://dx.doi.org/10.3390/v11070655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669721PMC
July 2019

Equine Influenza Virus in Asia: Phylogeographic Pattern and Molecular Features Reveal Circulation of an Autochthonous Lineage.

J Virol 2019 07 14;93(13). Epub 2019 Jun 14.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China

Equine influenza virus (EIV) causes severe acute respiratory disease in horses. Currently, the strains belonging to the H3N8 subtype are divided into two clades, Florida clade 1 (FC1) and Florida clade 2 (FC2), which emerged in 2002. Both FC1 and FC2 clades were reported in Asian and Middle East countries in the last decade. In this study, we described the evolution, epidemiology, and molecular characteristic of the EIV lineages, with focus on those detected in Asia from 2007 to 2017. The full genome phylogeny showed that FC1 and FC2 constituted separate and divergent lineages, without evidence of reassortment between the clades. While FC1 evolved as a single lineage, FC2 showed a divergent event around 2004 giving rise to two well-supported and coexisting sublineages, European and Asian. Furthermore, two different spread patterns of EIV in Asian countries were identified. The FC1 outbreaks were caused by independent introductions of EIV from the Americas, with the Asian isolates genetically similar to the contemporary American lineages. On the other hand, the FC2 strains detected in Asian mainland countries conformed to an autochthonous monophyletic group with a common ancestor dated in 2006 and showed evidence of an endemic circulation in a local host. Characteristic aminoacidic signature patterns were detected in all viral proteins in both Asian-FC1 and FC2 populations. Several changes were located at the top of the HA1 protein, inside or near antigenic sites. Further studies are needed to assess the potential impact of these antigenic changes in vaccination programs. The complex and continuous antigenic evolution of equine influenza viruses (EIVs) remains a major hurdle for vaccine development and the design of effective immunization programs. The present study provides a comprehensive analysis showing the EIV evolutionary dynamics, including the spread and circulation within the Asian continent and its relationship to global EIV populations over a 10-year period. Moreover, we provide a better understanding of EIV molecular evolution in Asian countries and its consequences on the antigenicity. The study underscores the association between the global horse movement and the circulation of EIV in this region. Understanding EIV evolution is imperative in order to mitigate the risk of outbreaks affecting the horse industry and to help with the selection of the viral strains to be included in the formulation of future vaccines.
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http://dx.doi.org/10.1128/JVI.00116-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580976PMC
July 2019

Molecular epidemiology of hepatitis B virus in Paraguay.

Infect Genet Evol 2019 07 23;71:91-97. Epub 2019 Mar 23.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Virología, Junín 956 4to piso, Ciudad Autónoma de Buenos Aires, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Electronic address:

Hepatitis B virus (HBV) infection is a leading cause of severe chronic liver disease worldwide. The HBV epidemiology in Latin American countries is complex and the data is still scanty and fragmentary. The aim of this study was to investigate the distribution of HBV genotypes in Paraguay and to estimate the viral population dynamic and spread pattern of the main phylogenetic group. To this end, partial and complete genome sequences were obtained from 60 blood donor candidates and analysed by phylogenetic and Bayesian phylodynamic approaches. The phylogenetic analysis based on sequences of partial Polymerase/Pre-S1 overlapping region showed a predominance of the Native American subgenotype F4 (81.7%), the presence of the European subgenotypes A2 (1.7%) and D3 (8.3%), the African subgenotype A1 (3, 5%) and the Asian subgenotypes B2 (1.7%) and C2 (1.7%). The distribution of HBV genotypes was in accordance with the ethnic composition of the population. The phylogeographic analysis of subgenotype F4 complete genomes suggests that this lineage emerged and spread in the last 300 years. Paraguay was the most probable location of the common ancestor. The lineage diverged into two main clades and spread to neighbor regions, mainly Bolivia and Northwest Argentina, and Buenos Aires. The phylogeny showed a scanty geographical structure and a complex migratory pattern. In conclusion, the HBV genotypes circulating in Paraguay reflect the ethnic origin of the population. The distribution of genotypes and the phylogeographic reconstruction showed the impact of both global and local migrations in shaping the HBV molecular epidemiology in the region.
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http://dx.doi.org/10.1016/j.meegid.2019.03.020DOI Listing
July 2019

SIGMA-VB: Validity and reliability of the Brazilian Portuguese version of the Montgomery-Åsberg Depression Rating Scale using the Structured Interview Guide for the MADRS.

Braz J Psychiatry 2019 Jul-Aug;41(4):297-302. Epub 2019 Feb 18.

Grupo de Estudos de Doenças Afetivas (GRUDA), Departamento de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil.

Objective: The Montgomery-Åsberg Depression Rating Scale (MADRS) is widely used to assess depression severity. The Structured Interview Guide for the MADRS (SIGMA) was created to standardize MADRS assessment. The objective of this study was to translate and validate the original SIGMA into a Brazilian Portuguese version (SIGMA-VB).

Methods: We translated and cross-culturally validated the original SIGMA into the SIGMA-VB, and assessed its psychometric properties using data from 93 adult outpatients enrolled in the Integral Assessment in Unipolar Depression (AIUNI) trial. Participants were assessed by two raters on five visits over 8 weeks. We calculated multiple interrater reliability indexes for the SIGMA-VB and used the Hamilton Depression Hating Scale (HAM-D) for validation purposes.

Results: According to the SIGMA-VB, participants had moderate depression at baseline followed by mild depression at 8 weeks. We found over 90% of correlation between scores attributed by different raters using the SIGMA-VB. Correlations between the SIGMA-VB and the HAM-D were above 66%.

Conclusion: Our findings confirm that the SIGMA-VB is a valid and reliable instrument to assess depression severity in clinical research and practice. Its interrater reliability was similar to that of a previously published Japanese version of the SIGMA.
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http://dx.doi.org/10.1590/1516-4446-2018-0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804310PMC
September 2019

Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure.

J Viral Hepat 2019 05 22;26(5):552-560. Epub 2019 Jan 22.

Facultad de Farmacia y Bioquímica, Cátedra de Virología, Universidad de Buenos Aires, Buenos Aires, Argentina.

The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes, induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy. The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants (ARMs) among individuals from Buenos Aires, Argentina. HBV surface antigen and polymerase sequences obtained from serum samples of 530 HBV-infected individuals were analysed. Samples belonged to genotypes A (28.1%), D (13.6%) and F (58.3%). VEMs, DMFs and ARMs were present in 40 (7.5%), 57 (10.7%) and 27 (5.1%) samples within the studied population. Additionally, eight nonpreviously reported VEMs and nine DFMs were identified. VEMs and DFMs were biased by genotype, being higher in genotype D (33.3% and 33.3%) compared to genotype A (6% and 17.4%) and genotype F (2.3% and 2.3%) (P > 0.001). On the contrary, there was no association between the presence of ARMs and HBV genotype (P = 0.324). VEMs, DFMs and ARMs create public health concerns. The current study provided valuable information about mutants in surface antigen and polymerase in HBV-infected patients from Argentina where HBV-F is the most prevalent genotype. Consequently, it constitutes an important reference for Latin American clinicians in order to optimize the management of HBV-infected patients.
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http://dx.doi.org/10.1111/jvh.13052DOI Listing
May 2019

Analysis of fitness differences of hepatitis B virus genotypes D and F using a cotransfection assay.

Arch Virol 2019 Feb 12;164(2):447-455. Epub 2018 Nov 12.

Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Hepatitis B virus (HBV) circulates as a collection of genetically related variants that evolve throughout the chronic infection. Those viral variants that have the greatest fitness are fixed. We recently showed different fitness for HBV variants involved in two epidemiological situations. To understand these fitness differences better, we determined the levels of extracellular HBV DNA, the synthesis of HBV DNA intermediates, and the expression of HBeAg and HBsAg in transfection and cotransfection assays. Our results show that for the subgenotype (sgt) D1, which has an 8-nucleotide deletion (sgtD1del) and exhibits lower fitness, the levels of extracellular DNA and intracellular replicative intermediates were much lower than with sgtD1wt or sgtD1mut (G1896A), which had higher fitness. In addition, in the cotransfection assay, sgtD1del inhibited sgtD1mut but not sgtD1wt replication. We also found that sgtF1b, which exhibits higher fitness, produces significantly higher levels of both extracellular DNA and intracellular replicative intermediates than does the lower-fitness sgtF4. These results demonstrate a relationship between fitness and the replicative ability of the HBV genome in the transfection assay. In addition, the data obtained by cotransfecting cells with sgtD1del and sgtD1mut provide new information about the impact of simultaneous replication of two viral variants in the same cell system on HBV replication.
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http://dx.doi.org/10.1007/s00705-018-4090-5DOI Listing
February 2019

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations.

PLoS One 2018 8;13(5):e0197109. Epub 2018 May 8.

Cátedra de Virología, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Hepatitis B virus (HBV) genotypes and mutants have been associated with differences in clinical and virological characteristics. Autophagy is a cellular process that degrades long-lived proteins and damaged organelles. Viruses have evolved mechanisms to alter this process to survive in host cells. In this work, we studied the modulation of autophagy by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4 replication induced accumulation of autophagosomes in hepatoma cells. However, no autophagic protein degradation was observed, indicating a blockage of autophagic flux at later stages. This inhibition of autophagy flux might be due to an impairment of lysosomal acidification in hepatoma cells. Moreover, HBV-mediated autophagy modulation was independent of the viral subgenotypes and enhanced in viruses with BCP and preCore naturally occurring mutations. These results contribute to understand the mechanisms by which different HBV variants contribute to the pathogenesis of HBV infections. In addition, this study is the first to describe the role that two highly prevalent naturally occurring mutations exert on the modulation of HBV-induced autophagy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197109PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940199PMC
August 2018

Evolutionary dynamics of Hepatitis C virus in a chronic HIV co-infected patient and its correlation with the immune status.

Infect Genet Evol 2018 09 4;63:30-38. Epub 2018 May 4.

Universidad de Buenos Aires, CONICET, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Buenos Aires, Argentina.

The HCV evolutionary dynamics play a key role in the infection onset, maintenance of chronicity, pathogenicity, and drug resistance variants fixation, and are thought to be one of the main caveats in the development of an effective vaccine. Previous studies in HCV/HIV co-infected patients suggest that a decline in the immune status is related with increases in the HCV intra-host genetic diversity. However, these findings are based on single point sequence diversity measures or coalescence analyses in several virus-host interactions. In this work, we describe the molecular evolution of HCV-E2 region in a single HIV-co-infected patient with two clearly defined immune conditions. The phylogenetic analysis of the HCV-1a sequences from the studied patient showed that he was co-infected with three different viral lineages. These lineages were not evenly detected throughout time. The sequence diversity and coalescence analyses of these lineages suggested the action of different evolutionary patterns in different immune conditions: a slow rate, drift-like process in an immunocompromised condition (low levels of CD4+ T lymphocytes); and a fast rate, variant-switch process in an immunocompetent condition (high levels of CD4+ T lymphocytes).
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http://dx.doi.org/10.1016/j.meegid.2018.05.003DOI Listing
September 2018

Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a multiethnic population of northeastern Argentina.

PLoS One 2018 12;13(1):e0190966. Epub 2018 Jan 12.

Laboratory of Molecular Anthropology, Department of Anthropology, University of Pennsylvania, Philadelphia, United States of America.

Background: Misiones Province in northeastern Argentina is considered to be a region with a high prevalence of HPV infection and a high mortality rate due to cervical cancer. The reasons for this epidemiological trend are not completely understood. To gain insight into this problem, we explored the relationship between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of cervical lesions/cancer in women from the city of Posadas in Misiones Province.

Methods: Two hundred and sixty-one women, including 92 cases of patients diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry was assessed through HVS1 sequencing, while the detection and typing of HPV infection was conducted through nested multiplex PCR analysis. Multivariate logistic regression was conducted with the resulting data to estimate the odds ratios (ORs) adjusted by socio-demographic variables.

Results: The study participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA ancestry, respectively. Multiple regression analysis showed that women with African mtDNAs were three times more likely to develop a cervical lesion than those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values were not significant when tested under more complex multivariate models. HPV infection and the development of cervical lesions/cancer were significant for all tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and HPV-58 [OR of 19.0 (2.4-147.7)].

Conclusion: HPV infection remains a central risk factor for cervical cancer in the Posadas population. The potential role of African mtDNA ancestry opens a new avenue for future medical association studies in multiethnic populations, and will require further confirmation in large-scale studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190966PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766133PMC
February 2018

Human hepatocytes apoptosis induced by replication of hepatitis B virus subgenotypes F1b and F4: Role of basal core promoter and preCore mutations.

Virology 2018 01 5;513:160-167. Epub 2017 Nov 5.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

In the context of pathogenesis of HBV infection, HBV genotypes and mutants have been shown to affect the natural course of chronic infection and treatment outcomes. In this work, we studied the induction of apoptosis by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. Both subgenotypes F1b and F4 HBV genome transfections induced cell death by apoptosis in human hepatocytes. The BCPdm (A1762T/G1764A) and preCore (G1896A) mutants induced higher levels of apoptosis than the wt virus. This increase in apoptosis was not associated with the enhanced viral replication of the variants. HBV-mediated apoptosis was independent of viral subgenotypes, and associated with the modulation of members of the regulatory Bcl-2 family proteins expression in the mitochondrial apoptotic pathway. Finally, the apoptosis induction increase observed for the preCore mutants suggests that HBeAg might have an anti-apoptotic effect in human hepatocytes.
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http://dx.doi.org/10.1016/j.virol.2017.10.016DOI Listing
January 2018

X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy.

Virus Res 2017 10 3;242:156-165. Epub 2017 Oct 3.

Universidad Nacional de Mar del Plata, Facultad de Ciencias Exactas y Naturales, Departamento de Química, Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address:

The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130-131 positions. The role of these mutations on HBV-X biological activity remains largely unknown. The aim of this study was to analyze the impact of the presence of different amino acids at 130-131 positions of HBV-X on the biological activity of the protein. Transient expression of wild type and mutant F1b and F4 HBV-X increased cell mortality by the induction of apoptosis in human hepatoma cells. The wild type and mutant HBV-X differentially modulate the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2 and Bcl-X) regulatory proteins of the Bcl-2 family. Furthermore, the expression of HBV-X variants of both subgenotypes induced autophagy of human tumoral hepatocytes. In conclusion, HBV-X variants of the Latin American HBV F genotype promotes human hepatocytes death by the induction of apoptosis and autophagy. The results of this work describe some of the molecular mechanisms by which HBV-X variants contribute to the pathogenesis of liver diseases in the infected liver and help to the biological characterization of genotype F, responsible of the majority of HBV infections in Argentina.
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http://dx.doi.org/10.1016/j.virusres.2017.09.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114566PMC
October 2017

Environmental Surveillance of Enteroviruses in Central Argentina: First Detection and Evolutionary Analyses of E14.

Food Environ Virol 2018 03 24;10(1):121-126. Epub 2017 Aug 24.

Facultad de Ciencias Médicas, Instituto de Virología "Dr. J. M. Vanella", Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n Ciudad Universitaria, 5016, Córdoba, Argentina.

Environmental surveillance is an effective approach to investigate the circulation of human enteroviruses in the population. Enteroviruses E14, CVA9, E-6, E16, E20, E25, E13, and CVA24 were detected in sewage and a watercourse in central Argentina. E14 was the most frequent serotype and was found for the first time in environmental samples in our region. Phylogenetic and coalescence analyses showed at least two recent introduction events.
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http://dx.doi.org/10.1007/s12560-017-9318-0DOI Listing
March 2018

Polymorphisms associated with resistance to protease inhibitors in naïve patients infected with hepatitis C virus genotype 1 in Argentina: Low prevalence of Q80K.

Virus Res 2017 08 31;240:140-146. Epub 2017 Aug 31.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address:

Incorporation of direct acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) significantly increases sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is no information about the prevalence of resistance-associated substitutions (RASs) in Argentina. The aim of this study was to analyze HCV variants resistant to protease inhibitors (PI) in naïve patients infected with HCV genotype 1 from Argentina. In this retrospective cross-sectional study, 103 patients infected with HCV-1 were included. Eighteen positions related with RASs were analyzed by Sanger at baseline and phylogenetic analysis was performed to determine the diversification of this samples. The analyzed RASs were present in 38 out of 103 patients (36.9%) infected with HCV-1. Patients infected with subtype HCV-1b had higher prevalence of baseline RASs than patients infected with HCV-1a [51.6% vs. 12.8%, respectively (p<0.001)]. The Q80K polymorphism was not found in HCV-1a samples, even when 51% of them belonged to cluster 1, which is associated with a high frequency of Q80K. Phylogenetic analysis showed that Argentinean samples were intermingled with sequences from other geographic regions. RASs to PI were highly prevalent and subtype dependent in treatment-naïve Argentinean patients. Surprisingly, Q80K polymorphism was not detected in our study population. The phylogenetic analysis showed no relationship between our samples and other samples from Brazil which also present a low prevalence of Q80K. This study supports the need for surveillance of resistance in patients who will be treated with DAA in each particular country since the observed RASs have very different prevalence worldwide.
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http://dx.doi.org/10.1016/j.virusres.2017.08.006DOI Listing
August 2017

HBV DNA genome co-transfection procedure for the evaluation of relative fitness.

PLoS One 2017 4;12(5):e0175543. Epub 2017 May 4.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Buenos Aires, Argentina.

Hepatitis B virus (HBV) has a high mutation rate and exists as a mixture of genetically different but closely related variants. We present a HBV DNA co-transfection fitness assay and use it to evaluate the relative fitness of different HBV variants in two scenarios: seroconversion process and occupation of an ecological niche. In the seroconversion experiment, subgenotype D1 (sgtD1) deletion (1763-1770) had significantly lower fitness comparing with both sgtD1 wild type and sgtD1mut G1896A, while, in the case of occupation of ecological niche experiment, the results showed the same relative fitness between all of the genotype combinations, except F1b-F4. In this case sgtF1b clearly overgrow sgtF4, which is in accordance with the observation that F1b is the most prevalent in the new infections in Argentina. In summary, we present a method aimed to evaluate HBV viral fitness which improve the analysis of the relative frequency of viral variants during the HBV infection process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175543PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417490PMC
September 2017

Investigation of associations between recurrence of major depressive disorder and spinal posture alignment: A quantitative cross-sectional study.

Gait Posture 2017 02 12;52:258-264. Epub 2016 Dec 12.

Mood Disorders Unit (GRUDA), Department of Psychiatry, School of Medicine, University of São Paulo, R. Dr. Ovídio Pires de Campos 785, 05403-010 São Paulo, Brazil.

The aim of this study was to investigate associations between poor spinal posture and the recurrence of major depressive episodes and severity of symptoms in patients with major depressive disorder (MDD). This was a cross-sectional quantitative study of MDD patients. Outpatients were recruited from consecutive admissions at a mood disorders unit of a tertiary psychiatric hospital. Of 136 MDD patients, 72 (53 women, 19 men; mean age, 42.4±9.1years) met all the criteria and completed the study. Forty-one patients were classified with a recurrent episode (RE) of MDD and 31 with a single episode (SE). Quantitative assessments of postural deviations were made using photogrammetry, including kyphosis, shoulder protraction, and head inclination. The severity of depressive episodes was assessed using the Hamilton Depression Rating Scale. The diagnosis and classification of patients were performed according to DSM-IV-TR and SCID criteria. Multivariate analysis of variance indicated that the RE group had greater anterior head inclination (35.39; SD: 1.57), greater scapular abduction (1.69; SD: 0.93), and worse thoracic kyphosis (139.38; SD: 1.19) than the SE group (p<0.001 for all). Multivariate analysis of covariance showed an interaction between the severity of depressive symptoms and the degree of thoracic kyphosis (p=0.002). Recurrence of depressive episodes is associated with measures of postural misalignment.
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http://dx.doi.org/10.1016/j.gaitpost.2016.12.011DOI Listing
February 2017

New pieces on genetic diversity and evolutionary history of hepatitis B virus: Characterization of the novel subgenotype F6.

Infect Genet Evol 2017 01 26;47:140-142. Epub 2016 Nov 26.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Junín 956 4to piso, Ciudad Autónoma de Buenos Aires, Argentina.; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Electronic address:

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http://dx.doi.org/10.1016/j.meegid.2016.11.023DOI Listing
January 2017

Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina.

PLoS One 2016 19;11(7):e0159509. Epub 2016 Jul 19.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina, Ciudad Autónoma de Buenos Aires, Argentina.

Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159509PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951016PMC
July 2017

Depressive Symptoms in Pregnancy: The Influence of Social, Psychological and Obstetric Aspects.

Rev Bras Ginecol Obstet 2016 Jun 11;38(6):293-300. Epub 2016 Jul 11.

Departament of Pediatrics and Puericulture, Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

Purpose To assess the prevalence of depressive symptoms and their association with social, psychological, behavioral and obstetric characteristics in pregnant women. Methods This is a cross-sectional study. The sample consisted of 375 pregnant women who attended prenatal clinics in two public maternity hospitals located in the city of Goiania, Brazil. To testify the depressive symptoms, we used the Hospital Anxiety and Depression Scale (HADS). A descriptive statistical analysis was performed using programs such as CDC EPI-INFO™, version 7.1.5, and Statistical Package for Social Sciences (IBM SPSS), version 21.0. Results the patients had probable depressive symptoms (15.47%) and possible depressive symptoms (25.33%). The bivariate analysis showed a significant association among "depressive symptoms" and the following variables: "single or divorced" (prevalence ratio, PR = 2.08; 95% confidence interval, CI = 1.26 to 3.44); "physical activity during pregnancy" (PR = 3.96; 95%CI = 1.28 to 12.31); exposure to "psychological/emotional" violence (PR = 4.74; 95%CI = 2.94 to 7.64); "prior mental problem" (PR = 2.66; 95%CI =1.49 to 4.73) and "obstetric complications during pregnancy" (PR = 2.53; 95%CI = 1.55 to 4.13). The multivariate analysis confirmed the association of these depressive symptoms with the variables "suffered psychological/emotional violence" (odds ratio, OR = 5.821; 95%CI = 2.939 to 11.528); "physical activity during pregnancy" (OR = 3.885; 95%CI = 1.060 to 14.231); "obstetric complications during pregnancy" (OR = 2.442; 95%CI = 1.233 to 4.834) and "single or divorced" (OR = 2.943; 95%CI = 1.326 to 6.533). Conclusions the prevalence of depressive symptoms among pregnant women is of 15.47%, and emotional violence is the main factor associated with gestational depression.
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http://dx.doi.org/10.1055/s-0036-1585072DOI Listing
June 2016

Molecular epidemiology of hepatitis B virus in Misiones, Argentina.

Infect Genet Evol 2016 10 16;44:34-42. Epub 2016 Jun 16.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4to Piso, Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The aims of this study were to describe the molecular epidemiology of HBV in the Province of Misiones, Argentina and estimate the phylodynamic of the main groups in a Bayesian coalescent framework. To this end, partial or complete genome sequences were obtained from 52 blood donor candidates. The phylogenetic analysis based on partial sequences of S/P region showed a predominance of genotype D (65.4%), followed by genotype F (30.8%) and genotype A as a minority (3.8%). At subgenotype level, the circulation of subgenotypes D3 (42.3%), D2 (13.5%), F1b (11.5%) and F4 (9.6%) was mainly identified. The Bayesian coalescent analysis of 29 complete genome sequences for the main groups revealed that the subgenotypes D2 and D3 had several introductions to the region, with ancestors dating back from 1921 to 1969 and diversification events until the late '70s. The genotype F in Misiones has a more recent history; subgenotype F4 isolates were intermixed with sequences from Argentina and neighboring countries and only one significant cluster dated back in 1994 was observed. Subgenotype F1b isolates exhibited low genetic distance and formed a closely related monophyletic cluster, suggesting a very recent introduction. In conclusion, the phylogenetic and coalescent analyses showed that the European genotype D has a higher circulation, a longer history of diversification and may be responsible for the largest proportion of chronic HBV infections in the Province of Misiones. Genotype F, especially subgenotype F1b, had a more recent introduction and its diversification in the last 20years might be related to its involvement in new transmission events.
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http://dx.doi.org/10.1016/j.meegid.2016.06.032DOI Listing
October 2016

Compartmentalization of hepatitis C virus variants in patients with hepatocellular carcinoma.

Mol Carcinog 2017 02 31;56(2):371-380. Epub 2016 May 31.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Chronic Hepatitis C Virus (HCV) infection is a major risk for hepatocellular carcinoma (HCC) development. HCV Core protein has been associated with the modulation of potentially oncogenic cellular processes and E2 protein has been useful in evolutive studies to analyze the diversity of HCV. Thus, the aim of this study was to evaluate HCV compartmentalization in tumoral, non-tumoral liver tissue and serum and to identify viral mutations potentially involved in carcinogenesis. Samples were obtained from four patients with HCC who underwent liver transplantation. Core and E2 were amplified, cloned and sequenced. Phylogenies and BaTS Test were performed to analyze viral compartmentalization and a signature sequence analysis was conducted by VESPA. The likelihood and Bayesian phylogenies showed a wide degree of compartmentalization in the different patients, ranging from total clustering to a more scattered pattern with small groups. Nevertheless, the association test showed compartmentalization for the three compartments and both viral regions tested in all the patients. Signature amino acid pattern supported the compartmentalization in three of the cases for E2 protein and in two of them for Core. Changes observed in Core included polymorphism R70Q/H previously associated with HCC. In conclusion, evidence of HCV compartmentalization in the liver of HCC patients was provided and further biological characterization of these variants may contribute to the understanding of carcinogenesis mediated by HCV infection. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/mc.22500DOI Listing
February 2017

Identification of a new clade of hepatitis B virus genotype F.

Infect Genet Evol 2015 Aug 12;34:122-5. Epub 2015 Jun 12.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4to piso, Ciudad Autónoma de Buenos Aires, Argentina.

Hepatitis B virus (HBV) is classified into eight main genotypes (A-H) and several subgenotypes. Here, three new genotype F complete genome sequences isolated from patients from Buenos Aires city are reported. The new sequences form a separate monophyletic group from the previously known subgenotype F4 strains. Based on results of phylogenetic, genetic distance and evolutionary analyses, the name F4b is proposed for these isolates and F4a for the formerly known as F4. The identification of new clusters allows deepening the knowledge about the diversification process and evolutionary history of HBV.
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http://dx.doi.org/10.1016/j.meegid.2015.06.007DOI Listing
August 2015

Inter and intrapatient evolution of hepatitis C virus.

Ann Hepatol 2015 Jul-Aug;14(4):442-9

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas CONICET.

Hepatitis C virus (HCV) has a short replication time, high mutation rates and large population sizes, all of which make it an excellent experimental model for evolution studies, because evolution can be visualized in real-time. In this review, we discuss the implications to study HCV evolution at the interpatient and intrapatient levels of infection. The HCV interpatient dynamics is relatively slow, because the generation time is generally long. Then, at population level, the HCV diversity originated by the high mutation and replication rates is modulated by the bottleneck at transmission. Thus, when the virus is transmitted to other hosts, viral diversity is reduced as a result of the founder effect. On the other hand, during intrapatient infection, HCV evolves rapidly, resulting in quasispecies. Accumulated evidence suggests that this quasispecies composition of the HCV population within the same individual may allow the virus to evade the immune response or escape treatment, leading to chronic infection. Thus, a better understanding of the complexities underlying the molecular evolution of HCV in natural populations is needed before accurate predictions of viral evolution can be made. In summary, HCV evolves both within and among patients. Consequently, HCV evolution should be studied at both levels in order to better understand the natural history of the virus and its potential implications in epidemiology, outcome of infection and progression of liver disease.
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February 2016

Hepatitis B virus genotype distribution and genotype-specific BCP/preCore substitutions in acute and chronic infections in Argentina.

PLoS One 2015 30;10(3):e0121436. Epub 2015 Mar 30.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Aim: In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections).

Results: Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896.

Discussion: HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121436PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378996PMC
March 2016

Changing epidemiology of hepatitis C virus genotypes in the central region of Argentina.

Arch Virol 2015 Apr 13;160(4):909-15. Epub 2015 Mar 13.

Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

The aim of this study was to analyze the prevalence of hepatitis C virus (HCV) genotypes in Córdoba province, Argentina, over a 12-year period and to study the changes at the molecular level. The HCV genotype was determined in 357 HCV-infected patients, and the phylogeny and demographic reconstruction for HCV-1 was assessed. A significant reduction in HCV-2 prevalence with respect to HCV-1 in Córdoba after 2003 was observed. These findings are consistent with the epidemiological changes observed in South America. Nevertheless, the consequences of these changes remain to be elucidated.
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http://dx.doi.org/10.1007/s00705-015-2390-6DOI Listing
April 2015

Genetic characterization and clinical implications of human papillomavirus type 16 (HPV16) variants from northeastern Argentina.

Infect Genet Evol 2015 Jan 20;29:103-9. Epub 2014 Nov 20.

Laboratorio de Biología Molecular Aplicada, Facultad de Ciencias Exactas, Quimicas y Naturales, Universidad Nacional de Misiones, Av. Mariano Moreno 1375, Posadas 3300, Misiones, Argentina.

Background: Human papillomavirus type 16 (HPV16) plays a central role in the development of cervical cancer. Worldwide studies indicate the existence of HPV16 variants that show different geographic distributions and oncogenic potential.

Objective: Our goal was to describe the genetic variation of HPV16 isolates identified in urban women with different grades of cervical lesions living in northeastern Argentina.

Study Design: We analyzed 116 HPV16-positive cervical samples (16 NLIM, 62 L-SIL, 16 H-SIL and 22 cervical cancer) from patients attending health centers in Misiones (Argentina) during 2006-13. HPV16 isolates were genetically characterized through PCR amplification and direct sequencing of 364 bp within the long control region, and the resulting sequences classified into variants based on phylogenetic analysis (lineages A, B, C and D). A potential association between HPV16 variants and lesion grade was evaluated through an odds ratio (OR) test. A temporal framework for the origin of HPV16 variants was assessed through coalescence analysis (BEAST v 1.7.5).

Results: Phylogenetic analysis of HPV16 sequences showed that 92.1% of the samples clustered with lineage A, and 6.9% to lineage D. HPV16 variants from lineage D were more frequently associated with high-grade lesions and cancer (HSIL+) than lineage A variants at an OR of 13.8 (1.6-117.0). The time to most common recent ancestor (tMCRA) of all variants was 119,103 years before present (HPD 95%=48,486-197,239), a date consistent with the time frame for modern human evolution.

Conclusion: Our results suggest that HPV16 variants from lineage D may represent an additional risk factor for the development of cervical cancer in women living in northeastern Argentina. This study provides new information about viral isolates present in Argentina that will contribute to the monitoring of HPV16 infection in the vaccine era.
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http://dx.doi.org/10.1016/j.meegid.2014.11.013DOI Listing
January 2015

Genetic diversity and clinical impact of human rhinoviruses in hospitalized and outpatient children with acute respiratory infection, Argentina.

J Clin Virol 2014 Dec 20;61(4):558-64. Epub 2014 Oct 20.

Virology Unit and Clinical Virology Laboratory, Hospital Universitario CEMIC, Av. Galván 4102, Buenos Aires, Argentina.

Background: Human rhinoviruses (HRV) are recognized as a cause of upper and lower acute respiratory infections (ARI). The circulating species and their clinical impact were not described in Argentina.

Objectives: To describe the molecular epidemiology of HRV in children and to determine the association of HRV species with outcome and severity.

Study Design: Hospitalized and outpatients children <6 years old with ARI without comorbidities (n=620) were enrolled (2008-2010). Demographic, clinical data and outcome were analyzed. HRV were identified by RT-PCR. Phylogenetic analysis and demographic reconstruction for HRV were performed in selected samples.

Results: HRV were detected in 252/620 (40.6%) of children; 8.5% in viral coinfection. Bronchiolitis (55%) and pneumonia (13%) were the most frequent clinical diagnosis. Of 202 inpatients with HRV: 72% required oxygen supplementation, 11% intensive care unit and 3% mechanical ventilation. HRV were identified as a risk factor for hospitalization (OR: 2.47). All three HRV species were detected being HRV-A (55%) and HRV-C (43%) the most frequent; HRV-B was infrequent (2%). Of 44 sequenced HRV, 30 genotypes were detected. Seven of them were the most prevalent and circulated during limited periods of time. The demographic reconstruction revealed a constant population size and a high turnover rate of genotypes. Demographic and clinical outcome were similar for HRV-A and HRV-C infections.

Conclusion: This study highlights the clinical impact of HRV in children without comorbidities as a cause of lower ARI and hospitalization. The high frequency of HRV infections may be associated with the simultaneous circulation of genotypes and their high turnover rate.
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http://dx.doi.org/10.1016/j.jcv.2014.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185656PMC
December 2014
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