The Role of Interferons in Rotavirus Infections and Protection

VanCott, John L.; McNeal, Monica; Choi, Anthony H.-C.; Ward, Richard L.

doi:10.1089/107999003321532501

Cited by 62 publications

(66 citation statements)

References 43 publications

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“…A similar response has also been reported with rotavirus infections in stat1 Ϫ/Ϫ mice, which are resistant to subsequent challenge (56 Ϫ/Ϫ mice are likely highly susceptible to nonvaccine strains of VACV (e.g., Copenhagen or Western Reserve strains). These data suggest that humans with mutations in stat1 could be contraindicated to vaccination with Dryvax and ACAM2000 and that following MVA vaccination, they may not receive the same level of protection as fully immunocompetent individuals.…”

Section: Discussionsupporting

confidence: 73%

A Mouse Model of Lethal Infection for Evaluating Prophylactics and Therapeutics against Monkeypox Virus

Stabenow¹,

Buller²,

Schriewer³

et al. 2010

J Virol

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Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola, the etiological agent of smallpox. In humans, MPXV causes a disease similar to smallpox and is considered to be an emerging infectious disease. Moreover, the use of MPXV for bioterroristic/biowarfare activities is of significant concern. Available small animal models of human monkeypox have been restricted to mammals with poorly defined biologies that also have limited reagent availability. We have established a murine MPXV model utilizing the STAT1-deficient C57BL/6 mouse. Here we report that a relatively low-dose intranasal (IN) infection induces 100% mortality in the stat1 ؊/؊ model by day 10 postinfection with high infectious titers in the livers, spleens, and lungs of moribund animals. Vaccination with modified vaccinia virus Ankara (MVA) followed by a booster vaccination is sufficient to protect against an intranasal MPXV challenge and induces an immune response more robust than that of a single vaccination. Furthermore, antiviral treatment with CMX001 (HDP-cidofovir) and ST-246 protects when administered as a regimen initiated on the day of infection. Thus, the stat1 ؊/؊ model provides a lethal murine platform for evaluating therapeutics and for investigating the immunological and pathological responses to MPXV infection.

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Section: Discussionsupporting

confidence: 73%

A Mouse Model of Lethal Infection for Evaluating Prophylactics and Therapeutics against Monkeypox Virus

Stabenow¹,

Buller²,

Schriewer³

et al. 2010

J Virol

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“…Using adult mice Zinkernagel and coworkers observed no significant effect of IFN-treatment on rotavirus induced diarrhoea and viral replication in these IFN-mutant mice (11)(12)(13). In this regard, age-related studies in mice, which were infected with rotavirus, revealed an age restriction of clinical symptoms (24,25) and therefore this data cannot be easily transferred to our model of infection of the newborn.…”

Section: Discussionmentioning

confidence: 95%

Type-I But Not Type-II Interferon Receptor Knockout Mice Are Susceptible to Biliary Atresia

et al. 2006

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ABSTRACT:The etiology of biliary atresia (BA) is not yet understood, but recent studies have shown inflammation with an upregulated interferon (IFN) activity in the intra-and extrahepatic bile ducts of patients with BA. These findings support an inflammatory/ infectious cause of BA as mimicked in our infective murine model. To study the role of the IFN receptors in our model, we used mice with inactivated INF-alpha/beta receptor A129, with inactivated IFNgamma receptor G129, or inactivation of both interferon receptors AG129 as well as the wild type controls W129. Mice were infected with rotavirus within 48h of birth and 7 d postpartum. The incidence of BA in each group was determined during a 3 wk period. In the second week the virus load was measured. BA incidence was 76% in A129 and 67% in AG129 animals, whereas in the G129 group only 33% of the pups developed BA. The wild type presented with a BA-incidence of 15%, while 7 d old mice failed to develop BA. There was no significant difference in the virus load of the livers between the groups independent of clinical symptoms. In conclusion, inactivation of type I INF-receptor significantly increases the incidence of BA following postpartal rotavirus infection. This effect is independent of the presence of type II-INF-receptors. Thus, in our model a type I IFN-linked deregulation of the innate immune system appears to be crucial for the induction of biliary atresia.

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“…Cytokines measured in cell culture supernatants or through intracellular (34,39,40). Previously, elevated levels of both IL-6 and IFN-␥ were reported in studies with rotavirus-infected human patients (12,13,15,31).…”

Section: Discussionmentioning

confidence: 99%

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

Sestak

McNeal

Choi

et al. 2004

J Virol

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The appearance of virus-specific CD4؉ and/or CD8 ؉ T lymphocytes in peripheral blood of captive juvenile rhesus macaques (Macaca mulatta) was observed following rotavirus infection. These cell-mediated immune responses were measured following experimental or natural infection after rotavirus was isolated from stool specimens of asymptomatic animals. The virus isolated was a new strain of simian rotavirus that we named TUCH (for Tulane University and Cincinnati Children's Hospital). Restimulation of peripheral T lymphocytes by inactivated double-or triple-layered TUCH rotavirus particles containing either VP6 or VP4 and VP7 on their respective surfaces resulted in increased quantities of interleukin-6 (IL-6) and IL-12 in cell culture supernatants. Recall responses to rotavirus by CD4 ؉ and CD8 ؉ T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon. Antigen presentation of TUCH rotavirus to lymphocytes was mediated via differentiated cultures of monocyte-derived dendritic (HLA-DR ؉ ) cells. This is the first report demonstrating cell-mediated immune responses to rotavirus in nonhuman primates. Further exploration of rhesus macaques in vaccine trials with human rotavirus vaccine candidates is the major objective of future studies.In the United States, rotavirus infection of 6-to 36-monthold children results in more than 50,000 hospitalizations each year (41). Throughout the world, at least 500,000 children die annually due to rotavirus-induced dehydration (25,28,41). Although extensive trials of novel vaccine candidates were performed with gnotobiotic piglets or genetically defined mice (28,41,44), none of these candidates have been evaluated in primates. Therefore, development of a nonhuman primate (NHP) model for evaluation of human rotavirus vaccine candidates is urgently needed. Although several NHP species, including chimpanzees and baboons as well as rhesus, vervet, pigtailed, and squirrel monkeys, have been reported to seroconvert to rotavirus with high, virus-specific antibody titers, no studies on cell-mediated immune responses have been conducted with an NHP model in the context of rotavirus (11,14,29,36,43). One reason is that clinical disease associated with rotavirus infection in NHPs, which has been reported to be limited to the first days or weeks of life (20,21,29,36,42), is difficult to produce experimentally.In this study, the cell-mediated immunological responses to rotavirus infection in juvenile rhesus macaques that were housed in biosafety level 2 facilities of the Tulane National Primate Research Center (TNPRC) were evaluated. We anticipated that cell-mediated immune responses could be measured in these animals by the time passive maternally acquired immunity subsided, i.e., at between 4 and 6 months of age. Thus, we studied the T lymphocytes collected from peripheral blood of juvenile rhesus macaques after a detectable rotavirus infection. Based on recent studies with the adult mouse model (4, 5, 24), our hypothesis was that immunological memory in rotav...

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The Role of Interferons in Rotavirus Infections and Protection

Cited by 62 publications

References 43 publications

A Mouse Model of Lethal Infection for Evaluating Prophylactics and Therapeutics against Monkeypox Virus

A Mouse Model of Lethal Infection for Evaluating Prophylactics and Therapeutics against Monkeypox Virus

Type-I But Not Type-II Interferon Receptor Knockout Mice Are Susceptible to Biliary Atresia

Defining T-Cell-Mediated Immune Responses in Rotavirus-Infected Juvenile Rhesus Macaques

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