Publications by authors named "Carla Mavian"

33 Publications

Emergence of porcine delta-coronavirus pathogenic infections among children in Haiti through independent zoonoses and convergent evolution.

medRxiv 2021 Mar 25. Epub 2021 Mar 25.

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, coronavirus emergence in our species has been associated with zoonotic transmissions from animal reservoirs , underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family - , - human infections reported to date have been limited to alpha- and betacoronaviruses . We identify, for the first time, porcine deltacoronavirus (PDCoV) strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the and the glycoprotein genes by convergent evolution. In particular, structural analysis predicts that one of the changes in the Spike S1 subunit, which contains the receptor-binding domain, may affect protein's flexibility and binding to the host cell receptor. Our findings not only underscore the ability of deltacoronaviruses to adapt and potentially lead to human-to-human transmission, but also raise questions about the role of such transmissions in development of pre-existing immunity to other coronaviruses, such as SARS-CoV-2.
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http://dx.doi.org/10.1101/2021.03.19.21253391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010738PMC
March 2021

Collection of SARS-CoV-2 Virus from the Air of a Clinic Within a University Student Health Care Center and Analyses of the Viral Genomic Sequence.

Aerosol Air Qual Res 2020 Jun 25;20(6):1167-1171. Epub 2020 May 25.

Department of Environmental Engineering Sciences, University of Florida.

The progression of COVID-19 worldwide can be tracked by identifying mutations within the genomic sequence of SARS-CoV-2 that occur as a function of time. Such efforts currently rely on sequencing the genome of SARS-CoV-2 in patient specimens (direct sequencing) or of virus isolated from patient specimens in cell cultures. A pilot SARS-CoV-2 air sampling study conducted at a clinic within a university student health care center detected the virus vRNA, with an estimated concentration of 0.87 virus genomes L air. To determine whether the virus detected was viable ('live'), attempts were made to isolate the virus in cell cultures. Virus-induced cytopathic effects (CPE) were observed within two days post-inoculation of Vero E6 cells with collection media from air samples; however, rtRT-PCR tests for SARS-CoV-2 vRNA from cell culture were negative. Instead, three other fast-growing human respiratory viruses were isolated and subsequently identified, illustrating the challenge in isolating SARS-CoV-2 when multiple viruses are present in a test sample. The complete SAR-CoV-2 genomic sequence was nevertheless determined by Sanger sequencing and most closely resembles SARS-CoV-2 genomes previously described in Georgia, USA. Results of this study illustrate the feasibility of tracking progression of the COVID-19 pandemic using environmental aerosol samples instead of human specimens. Collection of a positive sample from a distance more than 2 m away from the nearest patient traffic implies the virus was in an aerosol.
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http://dx.doi.org/10.4209/aaqr.2020.02.0202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792982PMC
June 2020

Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets.

J Neurovirol 2021 Feb 6;27(1):101-115. Epub 2021 Jan 6.

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.

Despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) remain prevalent in subjects undergoing therapy. HAND significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. We investigated transcriptomic profiles in frontal cortex tissues of Simian immunodeficiency virus (SIV)-infected Rhesus macaques sacrificed at different stages of infection. Gene expression was compared among SIV-infected animals (n = 11), with or without CD8+ lymphocyte depletion, based on detectable (n = 6) or non-detectable (n = 5) presence of the virus in frontal cortex tissues. Significant enrichment in activation of monocyte and macrophage cellular pathways was found in animals with detectable brain infection, independently from CD8+ lymphocyte depletion. In addition, transcripts of four poly (ADP-ribose) polymerases (PARPs) were up-regulated in the frontal cortex, which was confirmed by real-time polymerase chain reaction. Our results shed light on involvement of PARPs in SIV infection of the brain and their role in SIV-associated neurodegenerative processes. Inhibition of PARPs may provide an effective novel therapeutic target for HIV-related neuropathology.
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http://dx.doi.org/10.1007/s13365-020-00927-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786889PMC
February 2021

Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements.

Int J Mol Sci 2020 Dec 23;22(1). Epub 2020 Dec 23.

Emerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USA.

Our evolutionary and structural analyses revealed that the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) spike gene is a complex mosaic resulting from several recombination events. Additionally, the fixation of variants has mainly been driven by purifying selection, suggesting the presence of conserved structural features. Our dynamic simulations identified two main long-range covariant dynamic movements of the novel glycoprotein, and showed that, as a result of the evolutionary duality, they are preserved. The first movement involves the receptor binding domain with the -terminal domain and the -terminal domain 2 and is maintained across human, bat and pangolin coronaviruses. The second is a complex network of long-range dynamics specific to SARS-CoV-2 involving the novel PRRA and the conserved KR*SF cleavage sites, as well as conserved segments in -terminal domain 3. These movements, essential for host cell binding, are maintained by hinges conserved across human, bat, and pangolin coronaviruses glycoproteins. The hinges, located around Threonine 333 and Proline 527 within the -terminal domain and -terminal domain 2, represent candidate targets for the future development of novel pan-coronavirus inhibitors. In summary, we show that while recombination created a new configuration that increased the covariant dynamic movements of the SARS-CoV-2 glycoprotein, negative selection preserved its inter-domain structure throughout evolution in different hosts and inter-species transmissions.
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http://dx.doi.org/10.3390/ijms22010080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794730PMC
December 2020

Authors' Reply to: Errors in Tracing Coronavirus SARS-CoV-2 Transmission Using a Maximum Likelihood Tree. Comment on "A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis".

JMIR Public Health Surveill 2020 11 11;6(4):e24661. Epub 2020 Nov 11.

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.

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http://dx.doi.org/10.2196/24661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688377PMC
November 2020

Differing impacts of global and regional responses on SARS-CoV-2 transmission cluster dynamics.

bioRxiv 2020 Nov 6. Epub 2020 Nov 6.

Although the global response to COVID-19 has not been entirely unified, the opportunity arises to assess the impact of regional public health interventions and to classify strategies according to their outcome. Analysis of genetic sequence data gathered over the course of the pandemic allows us to link the dynamics associated with networks of connected individuals with specific interventions. In this study, clusters of transmission were inferred from a phylogenetic tree representing the relationships of patient sequences sampled from December 30, 2019 to April 17, 2020. Metadata comprising sampling time and location were used to define the global behavior of transmission over this earlier sampling period, but also the involvement of individual regions in transmission cluster dynamics. Results demonstrate a positive impact of international travel restrictions and nationwide lockdowns on global cluster dynamics. However, residual, localized clusters displayed a wide range of estimated initial secondary infection rates, for which uniform public health interventions are unlikely to have sustainable effects. Our findings highlight the presence of so-called "super-spreaders", with the propensity to infect a larger-than-average number of people, in countries, such as the USA, for which additional mitigation efforts targeting events surrounding this type of spread are urgently needed to curb further dissemination of SARS-CoV-2.
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http://dx.doi.org/10.1101/2020.11.06.370999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654859PMC
November 2020

Employing Molecular Phylodynamic Methods to Identify and Forecast HIV Transmission Clusters in Public Health Settings: A Qualitative Study.

Viruses 2020 08 22;12(9). Epub 2020 Aug 22.

Department of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Molecular HIV surveillance is a promising public health strategy for curbing the HIV epidemic. Clustering technologies used by health departments to date are limited in their ability to infer/forecast cluster growth trajectories. Resolution of the spatiotemporal dynamics of clusters, through phylodynamic and phylogeographic modelling, is one potential strategy to develop a forecasting tool; however, the projected utility of this approach needs assessment. Prior to incorporating novel phylodynamic-based molecular surveillance tools, we sought to identify possible issues related to their feasibility, acceptability, interpretation, and utility. Qualitative data were collected via focus groups among field experts ( = 17, 52.9% female) using semi-structured, open-ended questions. Data were coded using an iterative process, first through the development of provisional themes and subthemes, followed by independent line-by-line coding by two coders. Most participants routinely used molecular methods for HIV surveillance. All agreed that linking molecular sequences to epidemiological data is important for improving HIV surveillance. We found that, in addition to methodological challenges, a variety of implementation barriers are expected in relation to the uptake of phylodynamic methods for HIV surveillance. The participants identified several opportunities to enhance current methods, as well as increase the usability and utility of promising works-in-progress.
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http://dx.doi.org/10.3390/v12090921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551766PMC
August 2020

Correction: A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis.

JMIR Public Health Surveill 2020 08 10;6(3):e22853. Epub 2020 Aug 10.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.

[This corrects the article DOI: 10.2196/19170.].
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http://dx.doi.org/10.2196/22853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445602PMC
August 2020

Sociodemographic, Ecological, and Spatiotemporal Factors Associated with Human Immunodeficiency Virus Drug Resistance in Florida: A Retrospective Analysis.

J Infect Dis 2021 Mar;223(5):866-875

Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida, USA.

Background: Persons living with human immunodeficiency virus (HIV) with resistance to antiretroviral therapy are vulnerable to adverse HIV-related health outcomes and can contribute to transmission of HIV drug resistance (HIVDR) when nonvirally suppressed. The degree to which HIVDR contributes to disease burden in Florida-the US state with the highest HIV incidence- is unknown.

Methods: We explored sociodemographic, ecological, and spatiotemporal associations of HIVDR. HIV-1 sequences (n = 34 447) collected during 2012-2017 were obtained from the Florida Department of Health. HIVDR was categorized by resistance class, including resistance to nucleoside reverse-transcriptase , nonnucleoside reverse-transcriptase , protease , and integrase inhibitors. Multidrug resistance and transmitted drug resistance were also evaluated. Multivariable fixed-effects logistic regression models were fitted to associate individual- and county-level sociodemographic and ecological health indicators with HIVDR.

Results: The HIVDR prevalence was 19.2% (nucleoside reverse-transcriptase inhibitor resistance), 29.7% (nonnucleoside reverse-transcriptase inhibitor resistance), 6.6% (protease inhibitor resistance), 23.5% (transmitted drug resistance), 13.2% (multidrug resistance), and 8.2% (integrase strand transfer inhibitor resistance), with significant variation by Florida county. Individuals who were older, black, or acquired HIV through mother-to-child transmission had significantly higher odds of HIVDR. HIVDR was linked to counties with lower socioeconomic status, higher rates of unemployment, and poor mental health.

Conclusions: Our findings indicate that HIVDR prevalence is higher in Florida than aggregate North American estimates with significant geographic and socioecological heterogeneity.
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http://dx.doi.org/10.1093/infdis/jiaa413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938178PMC
March 2021

A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis.

JMIR Public Health Surveill 2020 06 1;6(2):e19170. Epub 2020 Jun 1.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non-peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.

Objective: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community.

Methods: We used maximum likelihood-based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020.

Results: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations.

Conclusions: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.
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http://dx.doi.org/10.2196/19170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265655PMC
June 2020

Under-the-Radar Dengue Virus Infections in Natural Populations of Aedes aegypti Mosquitoes.

mSphere 2020 04 29;5(2). Epub 2020 Apr 29.

Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA

The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue mosquito vector, , and its microbiome, which has been shown to influence virus transmission success. We examined the "metavirome" of four populations of mosquitoes collected in 2016 to 2017 in Manatee County, FL. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a 2-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, and explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of the DENV4 infections in that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. Since 1999, dengue outbreaks in the continental United States involving local transmission have occurred only episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from countries where the disease is endemic. To date, the U.S. public health response to dengue outbreaks has been largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of DENV4 transmission to and maintenance within a local mosquito vector population in the continental United States in the absence of a human case during two consecutive years. Our data suggest that molecular surveillance of mosquito populations in high-risk, high-tourism areas of the United States may enable proactive, targeted vector control before potential arbovirus outbreaks.
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http://dx.doi.org/10.1128/mSphere.00316-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193045PMC
April 2020

A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption.

Proc Natl Acad Sci U S A 2020 05 16;117(18):9981-9990. Epub 2020 Apr 16.

Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136;

HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses constructed with individual envelope genes that were obtained from plasma of six individuals undergoing analytic treatment interruption (ATI). M-tropic viruses could also be enriched from post-ATI plasma using macrophage-specific (CD14) but not CD4+ T cell-specific (CD3) antibodies, suggesting that M-tropic viruses had a macrophage origin. Molecular clock analysis indicated that the establishment of M-tropic HIV-1 variants predated ATI. Collectively, these data suggest that macrophages are a viral reservoir in HIV-1-infected individuals on effective ART and that M-tropic variants can appear in rebounding viremia when treatment is interrupted. These findings have implications for the design of curative strategies for HIV-1.
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http://dx.doi.org/10.1073/pnas.1917034117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211992PMC
May 2020

Toxigenic evolution and establishment of reservoirs in aquatic ecosystems.

Proc Natl Acad Sci U S A 2020 04 30;117(14):7897-7904. Epub 2020 Mar 30.

Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610;

The spread of cholera in the midst of an epidemic is largely driven by direct transmission from person to person, although it is well-recognized that is also capable of growth and long-term survival in aquatic ecosystems. While prior studies have shown that aquatic reservoirs are important in the persistence of the disease on the Indian subcontinent, an epidemiological view postulating that locally evolving environmental contributes to outbreaks outside Asia remains debated. The single-source introduction of toxigenic O1 in Haiti, one of the largest outbreaks occurring this century, with 812,586 suspected cases and 9,606 deaths reported through July 2018, provided a unique opportunity to evaluate the role of aquatic reservoirs and assess bacterial transmission dynamics across environmental boundaries. To this end, we investigated the phylogeography of both clinical and aquatic toxigenic O1 isolates and show robust evidence of the establishment of aquatic reservoirs as well as ongoing evolution of isolates from aquatic sites. Novel environmental lineages emerged from sequential population bottlenecks, carrying mutations potentially involved in adaptation to the aquatic ecosystem. Based on such empirical data, we developed a mixed-transmission dynamic model of , where aquatic reservoirs actively contribute to genetic diversification and epidemic emergence, which underscores the complexity of transmission pathways in epidemics and endemic settings and the need for long-term investments in cholera control at both human and environmental levels.
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http://dx.doi.org/10.1073/pnas.1918763117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149412PMC
April 2020

Isolation of Mayaro Virus from a Venezuelan Patient with Febrile Illness, Arthralgias, and Rash: Further Evidence of Regional Strain Circulation and Possible Long-Term Endemicity.

Am J Trop Med Hyg 2019 12;101(6):1219-1225

Laboratory of Cellular Signaling and Parasite Biochemistry, Instituto de Estudios Avanzados (IDEA), Caracas, Venezuela.

Fifty-two febrile patients living in Barquisimeto, Venezuela, were screened for arbovirus infection by virus culture during an outbreak of what was thought to be Zika virus infection. We report identification of Mayaro virus (MAYV) on culture of plasma from one patient, an 18-year-old woman with acute febrile illness, arthralgias, and psoriasiform rash. The strain was sequenced and was found to be most closely related to a 1999 strain from French Guiana, which, in turn, was related to two 2014 strains from Haiti. By contrast, previously reported outbreak-related MAYV strains from a sylvatic area approximately 80 miles from where the case patient lived were most closely related to Peruvian isolates. The two strain groups show evidence of having diverged genetically approximately 100 years ago.
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http://dx.doi.org/10.4269/ajtmh.19-0357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896866PMC
December 2019

Mayaro as a Caribbean traveler: Evidence for multiple introductions and transmission of the virus into Haiti.

Int J Infect Dis 2019 Oct 2;87:151-153. Epub 2019 Aug 2.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA; Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA. Electronic address:

Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that is being recognized with increasing frequency in South America. As part of on-going surveillance of a school cohort in Haiti, we identified MAYV infections in 5 children across a 7-month time span, at two different school campuses. All had a history of fever, and three had headaches; none complained of arthralgias. On analysis of whole genome sequence data, three strains were genotype D, and two were genotype L; phylogenetic and molecular clock analysis was consistent with at least 3 independent introductions of the virus into Haiti, with ongoing transmission of a common genotype D strain in a single school. Our data highlight the clear potential for spread of the virus in the northern Caribbean and North America.
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http://dx.doi.org/10.1016/j.ijid.2019.07.031DOI Listing
October 2019

Emergence of Madariaga virus as a cause of acute febrile illness in children, Haiti, 2015-2016.

PLoS Negl Trop Dis 2019 01 10;13(1):e0006972. Epub 2019 Jan 10.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States of America.

Madariaga virus (MADV), also known as South American eastern equine encephalitis virus, has been identified in animals and humans in South and Central America, but not previously in Hispaniola or the northern Caribbean. MADV was isolated from virus cultures of plasma from an 8-year-old child in a school cohort in the Gressier/Leogane region of Haiti, who was seen in April, 2015, with acute febrile illness (AFI). The virus was subsequently cultured from an additional seven AFI case patients from this same cohort in February, April, and May 2016. Symptoms most closely resembled those seen with confirmed dengue virus infection. Sequence data were available for four isolates: all were within the same clade, with phylogenetic and molecular clock data suggesting recent introduction of the virus into Haiti from Panama sometime in the period from October 2012-January 2015. Our data document the movement of MADV into Haiti, and raise questions about the potential for further spread in the Caribbean or North America.
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http://dx.doi.org/10.1371/journal.pntd.0006972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328082PMC
January 2019

Islands as Hotspots for Emerging Mosquito-Borne Viruses: A One-Health Perspective.

Viruses 2018 12 25;11(1). Epub 2018 Dec 25.

Emerging Pathogens Institute University of Florida, Gainesville, FL 32611, USA.

During the past ten years, an increasing number of arbovirus outbreaks have affected tropical islands worldwide. We examined the available literature in peer-reviewed journals, from the second half of the 20th century until 2018, with the aim of gathering an overall picture of the emergence of arboviruses in these islands. In addition, we included information on environmental and social drivers specific to island setting that can facilitate the emergence of outbreaks. Within the context of the One Health approach, our review highlights how the emergence of arboviruses in tropical islands is linked to the complex interplay between their unique ecological settings and to the recent changes in local and global sociodemographic patterns. We also advocate for greater coordination between stakeholders in developing novel prevention and mitigation approaches for an intractable problem.
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http://dx.doi.org/10.3390/v11010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356932PMC
December 2018

Distribution and characterization of Shiga toxin converting temperate phages carried by Shigella flexneri in Hispaniola.

Infect Genet Evol 2018 11 31;65:321-328. Epub 2018 Jul 31.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA. Electronic address:

Shigella infections account for a considerable burden of acute diarrheal diseases worldwide and remain a major cause of childhood mortality in developing countries. Although, all four species of Shigella (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei) cause bacillary dysentery, historically only S. dysenteriae type 1 has been recognized as carrying the genes for Shiga toxin (stx). Recent epidemiological data, however, have suggested that the emergence of stx carrying S. flexneri strains may have originated from bacteriophage-mediated inter-species horizontal gene transfer in one specific geographical area, Hispaniola. To test this hypothesis, we analyzed whole genome sequences of stx-encoding phages carried by S. flexneri strains isolated in Haiti and S. flexneri S. boydii and S. dysenteriae strains isolated from international travelers who likely acquired the infection in Haiti or the Dominican Republic. Phylogenetic analysis showed that phage sequences encoded in the Shigella strains from Hispaniola were bacteriophage φPOC-J13 and they were all closely related to a phage isolated from a USA isolate, E. coli 2009C-3133 serotype O119:H4. In addition, despite the low genetic heterogeneity of phages from different Shigella spp. circulating in the Caribbean island between 2001 and 2014, two distinct clusters emerged in Haiti and the Dominican Republic. Each cluster possibly originated from phages isolated from S. flexneri 2a, and within each cluster several instances of horizontal phage transfer from S. flexneri 2a to other species were detected. The implications of the emergence of stx-producing non-S. dysenteriae type 1 Shigella species, such as S. flexneri, spans not only the basic science behind horizontal phage spread, but also extends to medical treatment of patients infected with this pathogen.
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http://dx.doi.org/10.1016/j.meegid.2018.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260934PMC
November 2018

Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014.

PLoS Negl Trop Dis 2018 05 31;12(5):e0006505. Epub 2018 May 31.

Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.

In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May-August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.
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http://dx.doi.org/10.1371/journal.pntd.0006505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997359PMC
May 2018

A new "American" subgroup of African-lineage Chikungunya virus detected in and isolated from mosquitoes collected in Haiti, 2016.

PLoS One 2018 10;13(5):e0196857. Epub 2018 May 10.

US Navy and Marine Corps Public Health Center, Portsmouth, Virginia, United States of America.

As part of on-going arboviral surveillance activity in a semi-rural region in Haiti, Chikungunya virus (CHIKV)-positive mosquito pools were identified in 2014 (the peak of the Caribbean Asian-clade epidemic), and again in 2016 by RT-PCR. In 2014, CHIKV was only identified in Aedes aegypti (11 positive pools/124 screened). In contrast, in sampling in 2016, CHIKV was not identified in Ae. aegypti, but, rather, in (a) a female Aedes albopictus pool, and (b) a female Culex quinquefasciatus pool. Genomic sequence analyses indicated that the CHIKV viruses in the 2016 mosquito pools were from the East-Central-South African (ECSA) lineage, rather than the Asian lineage. In phylogenetic studies, these ECSA lineage strains form a new ECSA subgroup (subgroup IIa) together with Brazilian ECSA lineage strains from an isolated human outbreak in 2014, and a mosquito pool in 2016. Additional analyses date the most recent common ancestor of the ECSA IIa subgroup around May 2007, and the 2016 Haitian CHIKV genomes around December 2015. Known CHIKV mutations associated with improved Ae. albopictus vector competence were not identified. Isolation of this newly identified lineage from Ae. albopictus is of concern, as this vector has a broader geographic range than Ae. aegypti, especially in temperate areas of North America, and stresses the importance for continued vector surveillance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196857PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944945PMC
August 2018

Madariaga Virus: Identification of a Lineage III Strain in a Venezuelan Child With Acute Undifferentiated Febrile Illness, in the Setting of a Possible Equine Epizootic.

Clin Infect Dis 2018 08;67(4):619-621

Department of Infectious Diseases and Tropical Medicine, Instituto Diagnóstico Barquisimeto (IDB)/ Biomedical Research Institute/IDB Hospital, Barquisimeto, Lara.

We report identification of Madariaga virus (MADV) in plasma and urine samples from a child with acute undifferentiated febrile illness in Venezuela. Our data document the occurrence of milder MADV infections (ie, without encephalitis), with a symptom complex that resembles that seen with other arboviral infections, including dengue and zika.
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http://dx.doi.org/10.1093/cid/ciy224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070041PMC
August 2018

Phylodynamic applications in 21 century global infectious disease research.

Glob Health Res Policy 2017 8;2:13. Epub 2017 May 8.

Department of Epidemiology, University of Florida, Gainesville, FL USA.

Background: Phylodynamics, the study of the interaction between epidemiological and pathogen evolutionary processes within and among populations, was originally defined in the context of rapidly evolving viruses and used to characterize transmission dynamics. The concept of phylodynamics has evolved since the early 21 century, extending its reach to slower-evolving pathogens, including bacteria and fungi, and to the identification of influential factors in disease spread and pathogen population dynamics.

Results: The phylodynamic approach has now become a fundamental building block for the development of comparative phylogenetic tools capable of incorporating epidemiological surveillance data with molecular sequences into a single statistical framework. These innovative tools have greatly enhanced scientific investigations of the temporal and geographical origins, evolutionary history, and ecological risk factors associated with the growth and spread of viruses such as human immunodeficiency virus (HIV), Zika, and dengue and bacteria such as Methicillin-resistant .

Conclusions: Capitalizing on an extensive review of the literature, we discuss the evolution of the field of infectious disease epidemiology and recent accomplishments, highlighting the advancements in phylodynamics, as well as the challenges and limitations currently facing researchers studying emerging pathogen epidemics across the globe.
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http://dx.doi.org/10.1186/s41256-017-0034-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683535PMC
May 2017

Emergence of recombinant Mayaro virus strains from the Amazon basin.

Sci Rep 2017 08 18;7(1):8718. Epub 2017 Aug 18.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.

Mayaro virus (MAYV), causative agent of Mayaro Fever, is an arbovirus transmitted by Haemagogus mosquitoes. Despite recent attention due to the identification of several cases in South and Central America and the Caribbean, limited information on MAYV evolution and epidemiology exists and represents a barrier to prevention of further spread. We present a thorough spatiotemporal evolutionary study of MAYV full-genome sequences collected over the last sixty years within South America and Haiti, revealing recent recombination events and adaptation to a broad host and vector range, including Aedes mosquito species. We employed a Bayesian phylogeography approach to characterize the emergence of recombinants in Brazil and Haiti and report evidence in favor of the putative role of human mobility in facilitating recombination among MAYV strains from geographically distinct regions. Spatiotemporal characteristics of recombination events and the emergence of this previously neglected virus in Haiti, a known hub for pathogen spread to the Americas, warrants close monitoring of MAYV infection in the immediate future.
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http://dx.doi.org/10.1038/s41598-017-07152-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562835PMC
August 2017

Ranavirus phylogenomics: Signatures of recombination and inversions among bullfrog ranaculture isolates.

Virology 2017 11 10;511:330-343. Epub 2017 Aug 10.

Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, USA. Electronic address:

Ranaviruses are emerging pathogens of fish, amphibians, and reptiles that threaten aquatic animal industries and wildlife worldwide. Our objective was to genetically characterize ranaviruses isolated during separate bullfrog Lithobates catesbeianus die-offs that occurred eight years apart on the same North American farm. The earlier outbreak was due to a highly pathogenic strain of common midwife toad virus (CMTV) previously known only from Europe and China. The later outbreak was due to a chimeric ranavirus that displayed a novel genome arrangement and a DNA backbone typical for Frog virus 3 (FV3) strains except for interspersed fragments acquired through recombination with the CMTV isolated earlier. Both bullfrog ranaviruses are more pathogenic than wild-type FV3 suggesting recombination may have resulted in the increased pathogenicity observed in the ranavirus isolated in the later outbreak. Our study underscores the role international trade in farmed bullfrogs may have played in the global dissemination of highly pathogenic ranaviruses.
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http://dx.doi.org/10.1016/j.virol.2017.07.028DOI Listing
November 2017

Fatal Systemic Salmonellosis in a Florida Manatee ( Trichechus manatus latirostris).

J Wildl Dis 2017 10 2;53(4):930-933. Epub 2017 May 2.

1 Marine Mammal Pathobiology Lab, Florida Fish and Wildlife Conservation Commission, 3700 54th Avenue S, St. Petersburg, Florida 33711, USA.

A subadult male Florida manatee ( Trichechus manatus latirostris) stranded dead on Florida's Atlantic coast in January 2015. Necropsy and histopathologic findings confirmed chronic systemic bacterial infection caused by Salmonella enterica serotype IV 50:z4,z23,:- involving renal, respiratory, lymphatic, and skeletal systems. This was a unique case of systemic salmonellosis in a Florida manatee.
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http://dx.doi.org/10.7589/2017-01-012DOI Listing
October 2017

Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream.

J Virol 2016 10 12;90(19):8768-79. Epub 2016 Sep 12.

Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, Madrid, Spain

Unlabelled: Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (Sparus aurata), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected S. aurata fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the Papillomaviridae family described in fish, provides evidence for a more ancient origin of this family than previously thought.

Importance: Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family Iridoviridae In the Mediterranean area, the gilthead sea bream (Sparus aurata), an important farmed fish, is frequently affected. Using next-generation sequencing, we have identified within S. aurata lymphocystis lesions the concurrent presence of an additional LCDV species (LCDV-Sa) as well as two novel viruses. These are members of polyomavirus and papillomavirus families, and here we report them to be frequently associated with the presence of lymphocysts in affected fish. Because papillomaviruses have not been described in fish before, these findings support a more ancient origin of this virus family than previously thought and evolutionary implications are discussed.
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http://dx.doi.org/10.1128/JVI.01369-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021401PMC
October 2016

Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus.

J Virol 2015 Oct 5;89(20):10702-6. Epub 2015 Aug 5.

Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, Spain

Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections.
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http://dx.doi.org/10.1128/JVI.01580-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580169PMC
October 2015

The genome sequence of ectromelia virus Naval and Cornell isolates from outbreaks in North America.

Virology 2014 Aug 5;462-463:218-26. Epub 2014 Jul 5.

Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Nicolas Cabrera 1, Campus de Cantoblanco, Madrid, Spain; Department of Medicine, University of Cambridge, United Kingdom. Electronic address:

Ectromelia virus (ECTV) is the causative agent of mousepox, a disease of laboratory mouse colonies and an excellent model for human smallpox. We report the genome sequence of two isolates from outbreaks in laboratory mouse colonies in the USA in 1995 and 1999: ECTV-Naval and ECTV-Cornell, respectively. The genome of ECTV-Naval and ECTV-Cornell was sequenced by the 454-Roche technology. The ECTV-Naval genome was also sequenced by the Sanger and Illumina technologies in order to evaluate these technologies for poxvirus genome sequencing. Genomic comparisons revealed that ECTV-Naval and ECTV-Cornell correspond to the same virus isolated from independent outbreaks. Both ECTV-Naval and ECTV-Cornell are extremely virulent in susceptible BALB/c mice, similar to ECTV-Moscow. This is consistent with the ECTV-Naval genome sharing 98.2% DNA sequence identity with that of ECTV-Moscow, and indicates that the genetic differences with ECTV-Moscow do not affect the virulence of ECTV-Naval in the mousepox model of footpad infection.
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http://dx.doi.org/10.1016/j.virol.2014.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139192PMC
August 2014

Genome Sequence of WAU86/88-1, a New Variant of Vaccinia Virus Lister Strain from Poland.

Genome Announc 2014 Jan 9;2(1). Epub 2014 Jan 9.

Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Campus de Cantoblanco, Madrid, Spain.

The poxviruses Warsaw Agricultural University 86 (WAU86) and 88-1 (WAU88-1) were isolated in 1986 to 1988 from separate outbreaks in laboratory mice in Poland and described as ectromelia virus isolates. The genome sequences of these poxviruses reveal that they are almost identical and represent a novel variant of the vaccinia virus Lister strain.
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http://dx.doi.org/10.1128/genomeA.01086-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886943PMC
January 2014