Publications by authors named "Johan Nordgren"

58 Publications

Molecular Epidemiology of Sapovirus in Children Living in the Northwest Amazon Region.

Pathogens 2021 Jul 30;10(8). Epub 2021 Jul 30.

Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Linköping University, 581 85 Linköping, Sweden.

Sapovirus is an important etiological agent of acute gastroenteritis (AGE), mainly in children under 5 years old living in lower-income communities. Eighteen identified sapovirus genotypes have been observed to infect humans. The aim of this study was to identify sapovirus genotypes circulating in the Amazon region. Twenty-eight samples were successfully genotyped using partial sequencing of the capsid gene. The genotypes identified were GI.1 ( = 3), GI.2 ( = 7), GII.1 ( = 1), GII.2 ( = 1), GII.3 ( = 5), GII.5 ( = 1), and GIV.1 ( = 10). The GIV genotype was the most detected genotype (35.7%, 10/28). The phylogenetic analysis identified sapovirus genotypes that had no similarity with other strains reported from Brazil, indicating that these genotypes may have entered the Amazon region via intense tourism in the Amazon rainforest. No association between histo-blood group antigen expression and sapovirus infection was observed.
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http://dx.doi.org/10.3390/pathogens10080965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400878PMC
July 2021

Replication in Human Intestinal Enteroids of Infectious Norovirus from Vomit Samples.

Emerg Infect Dis 2021 08;27(8):2212-2214

A typical clinical symptom of human norovirus infection is projectile vomiting. Although norovirus RNA and viral particles have been detected in vomitus, infectivity has not yet been reported. We detected replication-competent norovirus in 25% of vomit samples with a 13-fold to 714-fold increase in genomic equivalents, confirming infectious norovirus.
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http://dx.doi.org/10.3201/eid2708.210011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314841PMC
August 2021

Effect of Infant and Maternal Secretor Status on Rotavirus Vaccine Take-An Overview.

Viruses 2021 Jun 14;13(6). Epub 2021 Jun 14.

Division of Molecular Medicine and Virology, Department of Clinical and Biomedical Sciences, Linköping University, 58183 Linköping, Sweden.

Histo-blood group antigens, which are present on gut epithelial surfaces, function as receptors or attachment factors and mediate susceptibility to rotavirus infection. The major determinant for susceptibility is a functional FUT2 enzyme which mediates the presence of α-1,2 fucosylated blood group antigens in mucosa and secretions, yielding the secretor-positive phenotype. Secretors are more susceptible to infection with predominant rotavirus genotypes, as well as to the commonly used live rotavirus vaccines. Difference in susceptibility to the vaccines is one proposed factor for the varying degree of efficacy observed between countries. Besides infection susceptibility, secretor status has been found to modulate rotavirus specific antibody levels in adults, as well as composition of breastmilk in mothers and microbiota of the infant, which are other proposed factors affecting rotavirus vaccine take. Here, the known and possible effects of secretor status in both infant and mother on rotavirus vaccine take are reviewed and discussed.
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http://dx.doi.org/10.3390/v13061144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232156PMC
June 2021

Secretor status strongly influences the incidence of symptomatic norovirus infection in a genotype-dependent manner in a Nicaraguan birth cohort.

J Infect Dis 2021 Jun 15. Epub 2021 Jun 15.

Department of Microbiology and Parasitology, National Autonomous University of Nicaragua - León, León, Nicaragua.

Background: The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented.

Methods: Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by RT-qPCR and histo-blood group antigens (HBGA) were determined by phenotyping of saliva and blood. Hazards ratios (95% CI) and predictors of norovirus AGE outcome stratified by HBGA were estimated using Cox proportional hazards models.

Results: Of 1,353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months old and had a higher incidence of norovirus GII compared to non-secretor children (15.4 vs 4.1/100 child-years, P = 0.006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted OR=0.09, 95% CI 0.02-0.33) or non-GII.4 viruses (adjusted OR=0.2, 95% CI: 0.07-0.6) were less likely to have severe AGE compared to GII.4 infected children.

Conclusion: Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.
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http://dx.doi.org/10.1093/infdis/jiab316DOI Listing
June 2021

Epidemiology of enteric virus infections in children living in the Amazon region.

Int J Infect Dis 2021 Jul 28;108:494-502. Epub 2021 May 28.

Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Fiocruz, Avenida Brasil, Rio de Janeiro, RJ, Brazil. Electronic address:

Objectives: To verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix™ vaccination coverage in children from the Amazon region.

Design: Fecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix™ RVA vaccination data were recorded.

Results: Norovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0-2.3; P = 0.04) but not to RVA, norovirus or SaV infection.

Conclusions: Norovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene.
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http://dx.doi.org/10.1016/j.ijid.2021.05.060DOI Listing
July 2021

The 5-HT Receptor Affects Rotavirus-Induced Motility.

J Virol 2021 07 12;95(15):e0075121. Epub 2021 Jul 12.

Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Rotavirus infection is highly prevalent in children, and the most severe effects are diarrhea and vomiting. It is well accepted that the enteric nervous system (ENS) is activated and plays an important role, but knowledge of how rotavirus activates nerves within ENS and to the vomiting center is lacking. Serotonin is released during rotavirus infection, and antagonists to the serotonin receptor subtype 3 (5-HT receptor) can attenuate rotavirus-induced diarrhea. In this study, we used a 5-HT receptor knockout (KO) mouse model to investigate the role of this receptor in rotavirus-induced diarrhea, motility, electrolyte secretion, inflammatory response, and vomiting reflex. The number of diarrhea days ( = 0.03) and the number of mice with diarrhea were lower in infected 5-HT receptor KO than wild-type pups. investigation of fluorescein isothiocyanate (FITC)-dextran transit time showed that intestinal motility was lower in the infected 5-HT receptor KO compared to wild-type mice ( = 0.0023). Ussing chamber measurements of potential difference across the intestinal epithelia showed no significant difference in electrolyte secretion between the two groups. Immediate early gene cFos expression level showed no difference in activation of the vomiting center in the brain. Cytokine analysis of the intestine indicated a low effect of inflammatory response in rotavirus-infected mice lacking the 5-HT receptor. Our findings indicate that the 5-HT receptor is involved in rotavirus-induced diarrhea via its effect on intestinal motility and that the vagus nerve signaling to the vomiting center occurs also in the absence of the 5-HT receptor. The mechanisms underlying rotavirus-induced diarrhea and vomiting are not yet fully understood. To better understand rotavirus pathophysiology, characterization of nerve signaling within the ENS and through vagal efferent nerves to the brain, which have been shown to be of great importance to the disease, is necessary. Serotonin (5-HT), a mediator of both diarrhea and vomiting, has been shown to be released from enterochromaffin cells in response to rotavirus infection and the rotavirus enterotoxin NSP4. Here, we investigated the role of the serotonin receptor 5-HT, which is known to be involved in the nerve signals that regulate gut motility, intestinal secretion, and signal transduction through the vagus nerve to the brain. We show that the 5-HT receptor is involved in rotavirus-induced diarrhea by promoting intestinal motility. The findings shed light on new treatment possibilities for rotavirus diarrhea.
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http://dx.doi.org/10.1128/JVI.00751-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274622PMC
July 2021

SARS-CoV-2 rapid antigen test: High sensitivity to detect infectious virus.

J Clin Virol 2021 07 24;140:104846. Epub 2021 Apr 24.

Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, Sweden. Electronic address:

Background: The COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 infections that can be used in point of care settings to limit disease transmission.

Objective: We evaluated two rapid antigen immunochromatographic tests, Abbott Panbio™ COVID-19 Ag Rapid Test (Panbio) and Zhejiang Orient Gene/Healgen Biotech Coronavirus Ag rapid test cassette (Orient gene) for detection of infectious SARS-CoV-2.

Results: The tests were evaluated on nasopharyngeal samples taken from individuals having respiratory and/or COVID-19 related symptoms, which had been analyzed for SARS-CoV-2 RNA using real-time PCR. In total 156 PCR-positive, and 130 (Panbio) and 176 (Orient Gene) PCR-negative samples were analyzed. Overall sensitivity and specificity were 71.8% and 100% for Panbio and 79.5% and 74.4% for the Orient Gene test respectively. The false positives by the Orient Gene test were verified as SARS-CoV-2 negative by in-house real-time PCR assay and were negative for the four seasonal coronaviruses. Subgroup analysis revealed that the antigen tests had high sensitivity for samples with Ct-values <25 (>88%) and for samples containing infectious viruses as determined by cultivation on Vero cells, 94.1% and 97.1% for the Panbio and Orient gene tests, respectively. Furthermore, both tests had a sensitivity of <50 picogram for nucleocapsid protein. No sample with a Ct-value >27 was shown to contain infectious virus.

Conclusion: The results indicate that the rapid antigen tests, especially the Panbio tests may be a valuable tool to detect contagious persons during the ongoing pandemic.
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http://dx.doi.org/10.1016/j.jcv.2021.104846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105081PMC
July 2021

Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients.

medRxiv 2021 Apr 29. Epub 2021 Apr 29.

New information is emerging about SARS-CoV-2 epidemiology and immunity, but little of this information comes from low- and middle-income countries or from patients receiving care in the outpatient setting. The current study investigated the SARS-CoV-2 infection status and antibody responses in 157 patients seeking care for a respiratory disease suggestive of COVID-19 in private healthcare clinics during the first wave (June-October 2020) of infections in Nicaragua. We examined nasal swabs for the presence of viral RNA via RT-PCR and longitudinally collected sera for the changes in SARS-CoV-2 Spike antibody levels over six months. Among patients with confirmed SARS-CoV-2 infections, we evaluated if clinical symptoms were associated with age, hematological parameters and co-morbidities. The combination of PCR and paired serology identified 60 (38%) of the 157 outpatients as acute COVID-19. While both PCR and serology identified the majority (n = 38, 64%) of the acute infections, a notable number of outpatients were identified by RT-qPCR (n = 13, 22%) or by serology (n = 9, 14%) only. During the longitudinal study, we identified 6 new infections by serology among the 97 non-COVID-19 subjects. In conclusion, this study report that more than one third of the outpatients seeking care for acute respiratory disease during the first epidemic wave of SARS-CoV-2 in Nicaragua had an acute mild COVID-19 infection that correlate with prolonged humoral response. This immune response to the RBD antigen, more likely IgG dependent, significantly increased between the acute to convalescent and decay in the late convalescent but still remained seropositive.
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http://dx.doi.org/10.1101/2021.04.28.21256122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095214PMC
April 2021

Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor α Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua.

J Infect Dis 2021 02;223(2):278-286

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya.

Methods: To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays.

Results: After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively).

Conclusion: This study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.
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http://dx.doi.org/10.1093/infdis/jiaa364DOI Listing
February 2021

Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014-2018.

Sci Rep 2020 04 24;10(1):6965. Epub 2020 Apr 24.

Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, Brazil.

Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1/2 RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a-b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.
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http://dx.doi.org/10.1038/s41598-020-64025-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181595PMC
April 2020

The Impact of Human Genetic Polymorphisms on Rotavirus Susceptibility, Epidemiology, and Vaccine Take.

Viruses 2020 03 17;12(3). Epub 2020 Mar 17.

Division of Molecular Medicine and Virology, Department of Clinical and Biomedical Sciences, Linköping University, 58183 Linköping, Sweden.

Innate resistance to viral infections can be attributed to mutations in genes involved in the immune response, or to the receptor/ligand. A remarkable example of the latter is the recently described Mendelian trait resistance to clinically important and globally predominating genotypes of rotavirus, the most common agent of severe dehydrating gastroenteritis in children worldwide. This resistance appears to be rotavirus genotype-dependent and is mainly mediated by histo-blood group antigens (HBGAs), which function as a receptor or attachment factors on gut epithelial surfaces. HBGA synthesis is mediated by fucosyltransferases and glycosyltransferases under the genetic control of the (secretor), (Lewis), and genes on chromosome 19. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. This genetic diversity has an effect on genotype-specific susceptibility, molecular epidemiology, and vaccine take. Here, we will discuss studies on genetic susceptibility to rotavirus infection and place them in the context of population susceptibility, rotavirus epidemiology, vaccine take, and public health impact.
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http://dx.doi.org/10.3390/v12030324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150750PMC
March 2020

Norovirus infection and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil.

Infect Genet Evol 2020 08 9;82:104280. Epub 2020 Mar 9.

Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Fiocruz, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, Brazil.

Norovirus has emerged as an important viral agent of acute pediatric gastroenteritis, with a growing genetic diversity reported in the last decades. Histo-blood group antigens (HBGAs) present on the surface of enterocytes are susceptibility factors for norovirus infection and differ between populations which could affects the epidemiology and evolution of these viruses. This study investigated the frequency, incidence and genetic diversity of noroviruses in a cohort of rotavirus A vaccinated children in association to the host HBGA (Secretor/Lewis) genetic susceptibility profile. Norovirus genogroups I and II (GI/GII) were screened by RT-qPCR in 569 stool samples from 132 children followed-up from birth to 11 months of age during 2014--2018. Noroviruses were identified in 21.2% of children enrolled in this study, with a norovirus detection rate of 5.6% (32/569), in 17.1% and 4.7% of acute diarrheic episodes (ADE) and non-ADE, respectively. The norovirus incidence was 5.8 infections per 100 child-months. Partial nucleotide sequencing characterized six different norovirus genotypes, with GII.4 Sydney 2012 being detected in 50% associated with three different polymerase genotypes (GII·P31, GII·P16 and GII·P4 New Orleans 2009). FUT3 genotyping was yielded seven new mutations in this population. A significant association between symptomatic norovirus infection and secretor profile could be inferred.
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http://dx.doi.org/10.1016/j.meegid.2020.104280DOI Listing
August 2020

Neurotrophic Factors Protect the Intestinal Barrier from Rotavirus Insult in Mice.

mBio 2020 01 21;11(1). Epub 2020 Jan 21.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Increased intestinal permeability has been proposed as a mechanism of rotavirus-induced diarrhea. Studies with humans and mice have, however, shown that rotavirus leaves intestinal permeability unaffected or even reduced during diarrhea, in contrast to most bacterial infections. Gastrointestinal permeability is regulated by the vagus nerve and the enteric nervous system, which is composed of neurons and enteric glial cells (EGCs). We investigated whether the vagus nerve, serotonin (5-HT), EGCs, and neurotropic factors contribute to maintaining gut barrier homeostasis during rotavirus infection. Using subdiaphragmatic vagotomized and 5-HT receptor knockout mice, we found that the unaffected epithelial barrier during rotavirus infection is independent of the vagus nerve but dependent on 5-HT signaling through enteric intrinsic 5-HT receptors. Immunofluorescence analysis showed that rotavirus-infected enterocytes were in close contact with EGCs and enteric neurons and that the glial cell-derived neurotrophic factor (GDNF) was strongly upregulated in enterocytes of infected mice. Moreover, rotavirus and 5-HT activated EGCs (0.001). Using Ussing chambers, we found that GDNF and -nitrosoglutathione (GSNO) led to denser epithelial barriers in small intestinal resections from noninfected mice (0.01) and humans (0.001) and that permeability was unaffected in rotavirus-infected mice. GSNO made the epithelial barrier denser in Caco-2 cells by increasing the expression of the tight junction protein zona occludens 1 (0.001), resulting in reduced passage of fluorescein isothiocyanate dextran (0.05) in rotavirus-infected monolayers. This is the first report to show that neurotropic factors contribute to maintaining the gut epithelial barrier during viral insult. Human and mouse studies have shown that rotavirus infection is associated with low inflammation and unaffected intestinal barrier at the time of diarrhea, properties different from most bacterial and inflammatory diseases of the gut. We showed by , , and experiments that neurotrophic factors and 5-HT have barrier protective properties during rotavirus insult. These observations advance our understanding of how the gut barrier is protected against rotavirus and suggest that rotavirus affects the gut barrier differently from bacteria. This is the first report to show that neurotrophic factors contribute to maintain the gut epithelial barrier during viral insult.
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http://dx.doi.org/10.1128/mBio.02834-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974565PMC
January 2020

Secretor Status is Associated with Susceptibility to Disease in a Large GII.6 Norovirus Foodborne Outbreak.

Food Environ Virol 2020 03 29;12(1):28-34. Epub 2019 Oct 29.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain.
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http://dx.doi.org/10.1007/s12560-019-09410-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052033PMC
March 2020

Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants.

Sci Rep 2019 07 24;9(1):10764. Epub 2019 Jul 24.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (≤3, 4-7 and ≥8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at ≥4 days post vaccination (DPV). At ≥4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (>13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.
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http://dx.doi.org/10.1038/s41598-019-47166-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656718PMC
July 2019

Psychopathological symptoms associated with synthetic cannabinoid use: a comparison with natural cannabis.

Psychopharmacology (Berl) 2019 Sep 9;236(9):2677-2685. Epub 2019 Apr 9.

Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.

Background: Synthetic cannabinoids (SCs) are a class of new psychoactive substances that have been rapidly evolving around the world throughout recent years. Many different synthetic cannabinoid analogues are on the consumer market and sold under misleading names, like "spice" or "incense." A limited number of studies have reported serious health effects associated with SC use. In this study, we compared clinical and subclinical psychopathological symptoms associated with SC use and natural cannabis (NC) use.

Methods: A convenience sample of 367 NC and SC users was recruited online, including four validated psychometric questionnaires: The Drug Use Disorders Identification Test (DUDIT), Insomnia Severity Index (ISI), Altman Mania Scale (Altman), and Brief Symptom Inventory (BSI). The two groups were compared with analysis of variance (ANOVA) and covariance (ANCOVA), chi tests, and logistic regression when appropriate.

Results: The SC user group did not differ in age from the NC user group (27.7 years), but contained less females (21% and 30%, respectively). SC users scored higher than NC users on all used psychometric measures, indicating a higher likelihood of drug abuse, sleep problems, (hypo)manic symptoms, and the nine dimensions comprising the BSI, somatization, obsessive-compulsive behavior, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. Odds ratios (95% CI) for the SC user group vs NC user group were, respectively, drug dependence 3.56 (1.77-7.16), (severe) insomnia 5.01 (2.10-11.92), (hypo-)mania 5.18 (2.04-13.14), and BSI psychopathology 5.21 (2.96-9.17).

Discussion: This study shows that SC use is associated with increased mental health symptomatology compared to NC use.
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http://dx.doi.org/10.1007/s00213-019-05238-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695363PMC
September 2019

Genetic Susceptibility to Human Norovirus Infection: An Update.

Viruses 2019 03 6;11(3). Epub 2019 Mar 6.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden.

Noroviruses are the most common etiological agent of acute gastroenteritis worldwide. Despite their high infectivity, a subpopulation of individuals is resistant to infection and disease. This susceptibility is norovirus genotype-dependent and is largely mediated by the presence or absence of human histo-blood group antigens (HBGAs) on gut epithelial surfaces. The synthesis of these HBGAs is mediated by fucosyl- and glycosyltransferases under the genetic control of the (secretor), (Lewis) and genes. The so-called non-secretors, having an inactivated FUT2 enzyme, do not express blood group antigens and are resistant to several norovirus genotypes, including the predominant GII.4. Significant genotypic and phenotypic diversity of HBGA expression exists between different human populations. Here, we review previous in vivo studies on genetic susceptibility to norovirus infection. These are discussed in relation to population susceptibility, vaccines, norovirus epidemiology and the impact on public health.
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http://dx.doi.org/10.3390/v11030226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466115PMC
March 2019

Phenotyping of Lewis and secretor HBGA from saliva and detection of new FUT2 gene SNPs from young children from the Amazon presenting acute gastroenteritis and respiratory infection.

Infect Genet Evol 2019 06 18;70:61-66. Epub 2019 Feb 18.

Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Avenida Brasil, 4365-Manguinhos, Rio de Janeiro, RJ, Brazil.

The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b+) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a+b+) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A>T, 501C>T, 585C>T, 855A>T and missense substitutions 327C>T [S (Ser) > C (Cys)], 446 T>C [L(Leu) > P(Pro)], 723C>A [N(Asn) > K(Lys)], 724A>T [I(Ile) > F(Phe)], 736C>A [H(His) > N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes.
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http://dx.doi.org/10.1016/j.meegid.2019.02.011DOI Listing
June 2019

Molecular epidemiology and host genetics of norovirus and rotavirus infections in Portuguese elderly living in aged care homes.

J Med Virol 2019 06 20;91(6):1014-1021. Epub 2019 Feb 20.

Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Lisboa, Portugal.

Norovirus (NoV) and rotavirus group A (RVA) are major agents of acute gastroenteritis worldwide. This study aimed to investigate their epidemiological profile in Portuguese elderly living in long-term care facilities and to assess the host genetic factors mediating infection susceptibility. From November 2013 to June 2015, 636 faecal specimens from 169 elderly, mainly asymptomatic, living in nursing homes in Greater Lisbon and Faro district, Portugal, were collected. NoV and RVA were detected by real-time polymerase chain reaction and NoV genotyped by phylogenetic analysis. NoV detection rate was 7.1% (12 of 169). Three GI.3 and one GII.6 strains were genotyped. RVA detection rate was 3.6% (6 of 169), exclusively in asymptomatic individuals. Host genetic factors associated with infection susceptibility were described on 250 samples by saliva-based enzyme-linked immunosorbent assays. The Lewis-negative phenotype was 8.8% (22 of 250) and the rate of nonsecretors was 16.8% (42 of 250). Association to NoV and RVA infection was performed in the subgroup of individuals (n = 147) who delivered both faecal and saliva samples. The majority of NoV- and RVA-positive individuals (90.9% and 83.3%, respectively) were secretor-positive, with Lewis B phenotype. In a subset of individuals, FUT2 and FUT3 genes were genotyped to assess mutations and validate the secretor and Lewis phenotypes. All sequenced nonsecretors were homozygous for FUT2 nonsense mutation G428A. In this study, low detection rates of NoV and RVA infections were found during two winter seasons. However, even in the absence of any outbreak, the importance of finding these infections in a nonepidemic situation in long-term care facilities may have important implications for infection control.
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http://dx.doi.org/10.1002/jmv.25425DOI Listing
June 2019

Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection.

Sci Rep 2018 08 28;8(1):12961. Epub 2018 Aug 28.

CRCINA, Inserm, Université d'Angers, Université de Nantes, Nantes, France.

Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAcβ3Galβ4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of the FUT2 wild type allele in sera from young healthy adults. Nonetheless, in vitro infection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
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http://dx.doi.org/10.1038/s41598-018-31005-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113245PMC
August 2018

Detection of rotavirus- and norovirus-specific IgG memory B cells in tonsils.

J Med Virol 2019 02 16;91(2):326-329. Epub 2018 Jul 16.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.

Because rotavirus (RV) and norovirus (NoV) are transmitted through the fecal-oral route, tonsils due to their location within the oropharynx may sample or become infected with these viruses. We investigated if RV and NoV RNA/antigen, or virus-specific memory/plasma B cells can be detected in the tonsils. While neither RV/NoV antigen, nor genomic RNA was detected, 90% (27/30) of tonsils tested had RV- and NoV-specific IgG memory B cells. However, the mechanism explaining how these cells get there (whether because of local induction or homing after induction at other sites) and the role these cells might play during active infection is not yet clear.
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http://dx.doi.org/10.1002/jmv.25247DOI Listing
February 2019

Rotavirus and norovirus in children with severe diarrhea in Burkina Faso before rotavirus vaccine introduction.

J Med Virol 2018 09 25;90(9):1453-1460. Epub 2018 May 25.

Division of Molecular Virology, Linköping University, Linköping, Sweden.

Burkina Faso introduced rotavirus vaccine (RotaTeq) to the national immunization program in November 2013. This study describes the detection rates, clinical profiles, and molecular epidemiology of rotavirus and norovirus (NoV) infections among children <5 years hospitalized (n = 154) because of acute diarrhea in Ouagadougou, Burkina Faso, from December 2012 to November 2013, just before the start of vaccination. Overall, 44% and 23% of fecal samples were positive for rotavirus and NoV, respectively, most of them detected during the cold dry season (December-March). The predominant G/P combinations were G12P[8] (47%) and G6P[6] (30%). G2P[4] (n = 3), G12P[6] (n = 3), and G6P[8] (n = 1) were also detected. Nearly all (94%) successfully genotyped NoV strains belonged to genotype GII.4. The predominance of rotavirus and NoV was noteworthy in the age group ≤6 months, with 67% rotavirus and 22% NoV, respectively. Vomiting was significantly more common among rotavirus-infected children. To conclude, this study shows high detection rates of both rotavirus and NoV in children with severe diarrhea in Burkina Faso just before the introduction of rotavirus group A vaccination. The results can be used for estimating the impact of rotavirus group A vaccination, which started in the end of 2013. Furthermore, this study shows that the G6P[6] rotavirus strains emerging in Burkina Faso in 2010 is now established as a regionally important genotype.
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http://dx.doi.org/10.1002/jmv.25213DOI Listing
September 2018

The Lewis A phenotype is a restriction factor for Rotateq and Rotarix vaccine-take in Nicaraguan children.

Sci Rep 2018 01 24;8(1):1502. Epub 2018 Jan 24.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, 581 83, Linköping, Sweden.

Histo-blood group antigens (HBGAs) and the Lewis and secretor antigens are associated with susceptibility to rotavirus infection in a genotype-dependent manner. Nicaraguan children were prospectively enrolled in two cohorts vaccinated with either RotaTeq RV5 (n = 68) or Rotarix RV1 (n = 168). Lewis and secretor antigens were determined by saliva phenotyping and genotyping. Seroconversion was defined as a 4-fold increase in plasma IgA antibody titer 1 month after administration of the first dose of the vaccine. Regardless of the vaccine administered, significantly fewer of the children with Lewis A phenotype (0/14) seroconverted after receiving the first vaccine dose compared to 26% (45/175) of those with the Lewis B phenotype and 32% (15/47) of the Lewis negative individuals (P < 0.01). Furthermore, following administration of the RV1 vaccine, secretor-positive ABO blood group B children seroconverted to a significantly lesser extent (5%) compared to secretor-positive children with ABO blood groups A (26%) and O (27%) (P < 0.05). Other factors such as pre-vaccination titers, sex, breastfeeding, and calprotectin levels did not influence vaccine-take. Differences in HBGA expression appear to be a contributing factor in the discrepancy in vaccine-take and thus, in vaccine efficacy in different ethnic populations.
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http://dx.doi.org/10.1038/s41598-018-19718-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784145PMC
January 2018

Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.

J Virol 2018 04 14;92(7). Epub 2018 Mar 14.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells. The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cells This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells.
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http://dx.doi.org/10.1128/JVI.00026-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972892PMC
April 2018

Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial.

PLoS One 2017 27;12(10):e0186824. Epub 2017 Oct 27.

Department of Clinical and Experimental Medicine, Division of Molecular Virology, Medical Faculty, Linköping University, Linköping, Sweden.

Background: Rotavirus and norovirus cause acute gastroenteritis with severe diarrhoea and vomiting, symptoms that may lead to severe dehydration and death. The objective of this randomized double-blinded placebo-controlled study was to investigate whether ondansetron, a serotonin receptor antagonist could attenuate rotavirus- and norovirus-induced vomiting and diarrhoea, which would facilitate oral rehydration and possibly accelerate recovery and reduce need for hospitalization.

Methods: Children with acute gastroenteritis, aged 6 months to 16 years where enrolled (n = 104) and randomized to one single oral dose (0.15mg/kg) of ondansetron (n = 52) or placebo (n = 52). The number of diarrhoea and vomiting episodes during the 24 hours following treatment was reported as well as the number of days with symptoms. Pathogens in faeces were diagnosed by real-time PCR. Outcome parameters were analyzed for rotavirus- and norovirus-positive children.

Results: One dose of oral ondansetron reduced duration of rotavirus clinical symptoms (p = 0.014), with a median of two days. Furthermore, ondansetron reduced diarrhea episodes, most pronounced in children that had been sick for more than 3 days before treatment (p = 0.028).

Conclusion: Ondansetron may be a beneficial treatment for children with rotavirus gastroenteritis.

Trial Registration: European Clinical Trial Database EudraCT 2011-005700-15.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186824PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659648PMC
November 2017

Pediatric norovirus GII.4 infections in Nicaragua, 1999-2015.

Infect Genet Evol 2017 11 2;55:305-312. Epub 2017 Oct 2.

Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Objectives: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015.

Methods: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children≤7years with AGE from 6 hospitals in Nicaragua (n=538), and 3 community clinics (n=919) and households (n=333) in León, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n=162) and households (n=105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene.

Results: Norovirus was found in 19% (n=338) and 12% (n=32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend.

Conclusions: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12months of age, implicating GII.4 as the main norovirus vaccine target.
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http://dx.doi.org/10.1016/j.meegid.2017.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911913PMC
November 2017

Rotavirus and Serotonin Cross-Talk in Diarrhoea.

PLoS One 2016 26;11(7):e0159660. Epub 2016 Jul 26.

Department of Clinical and Experimental Medicine, Division of Molecular Virology, Linköping University, Linköping, Sweden.

Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p < 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159660PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961431PMC
July 2017

Innate Resistance and Susceptibility to Norovirus Infection.

PLoS Pathog 2016 04 26;12(4):e1005385. Epub 2016 Apr 26.

Division of Molecular Virology, IKE, Medical Faculty, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1371/journal.ppat.1005385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845991PMC
April 2016

Molecular epidemiology of rotavirus in four provinces of Angola before vaccine introduction.

J Med Virol 2016 09 11;88(9):1511-20. Epub 2016 Mar 11.

Global Health and Tropical Medicine (GHTM), Medical Microbiology Unit, Institute of Hygiene and Tropical Medicine, NOVA University of Lisbon, Lisbon, Portugal.

Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. J. Med. Virol. 88:1511-1520, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24510DOI Listing
September 2016

The fecal virome of South and Central American children with diarrhea includes small circular DNA viral genomes of unknown origin.

Arch Virol 2016 Apr 19;161(4):959-66. Epub 2016 Jan 19.

Blood Systems Research Institute, San Francisco, CA, 94118, USA.

Viral metagenomics of feces collected from 58 Peruvian children with unexplained diarrhea revealed several small circular ssDNA genomes. Two genomes related to sequences previously reported in feces from chimpanzees and other mammals and recently named smacoviruses were characterized and then detected by PCR in 1.7 % (1/58) and 19 % (11/58) of diarrheal samples, respectively. Another three genomes from a distinct small circular ssDNA viral group provisionally called pecoviruses encoded Cap and Rep proteins with <35 % identity to those in related genomes reported in human, seal, porcine and dromedary feces. Pecovirus DNA was detected in 15.5 % (9/58), 5.9 % (3/51) and 3 % (3/100) of fecal samples from unexplained diarrhea in Peru, Nicaragua and Chile, respectively. Feces containing these ssDNA genomes also contained known human enteric viral pathogens. The cellular origins of these circular ssDNA viruses, whether human cells, ingested plants, animals or fungal foods, or residents of the gut microbiome, are currently unknown.
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http://dx.doi.org/10.1007/s00705-016-2756-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814309PMC
April 2016
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