The Immune Response to Astrovirus Infection

Abstract

Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of astrovirus infection and pathogenesis, little is known about the immune response to astrovirus infection. Studies from humans and animals suggest that adaptive immunity is important in restricting classic and novel astrovirus infections, while studies from animal models and cell culture systems suggest that an innate immune system plays a role in limiting astrovirus replication. The relative contribution of each arm of the immune system in restricting astrovirus infection remains unknown. This review summarizes our current understanding of the immune response to astrovirus infection and highlights some of the key questions that stem from these studies. A full understanding of the immune response to astrovirus infection is required to be able to treat and control astrovirus-induced gastroenteritis.

Astrovirus infections induce age-dependent dysbiosis in gut microbiomes of bats

“…The increase in gut microbial diversity in adult bats is similar to reported effects of virus infections that directly interfere with the host immune system and indirectly affect the host gut microbiome, such as during Human Immunodeficiency Virus (HIV) infection in humans [35], Simian Immunodeficiency Virus (SIV) infection in chimpanzees [28] or Canine Distemper Virus (CDV) infection in giant panda [29]. In adult bats, the increase in bacterial diversity might be the result of a better immune-mediated counter-response against AstV-infection, either simply because of the more effective immune system in adulthood or because of an acquired immunity against repeated AstVinfections [36]. This might be the reason that AstV-infections in children cause more pathological symptoms and higher disease severity than in adults [3].…”

Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape

“…Previous in vitro reports also demonstrated the sensitivity of AstV infection to innate immune responses. Specifically, HAstV replication induces type I interferon (IFN) responses later during infection in vitro [61], and pre-treatment of Caco-2 cells with type I IFN reduces viral genome loads, viral protein synthesis, and the virus-induced barrier permeability [32]. Conversely, neutralization of type I IFNs or inhibition of the Tank-binding kinase 1 (TBK1), a mediator in the IFN signaling cascade, increased viral titers.…”

Immunogenicity and Efficacy Evaluation of Subunit Astrovirus Vaccines

“…In this study, significantly higher anti-MAstV serum antibody detected in mice and mink showed that CP truncates could elicit a reasonable systematic humoral immune response compared to full-length CP. Humoral immunity plays an important role in protecting against AstVs since the presence of protective antibodies against HAstV in healthy adults provides a mechanism of protection against reinfection [46,47]. The development of anti-AstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the AstV capsid surface [48] and the immunosuppressing peptides along AstV CP [46,49,50].…”

“…Humoral immunity plays an important role in protecting against AstVs since the presence of protective antibodies against HAstV in healthy adults provides a mechanism of protection against reinfection [46,47]. The development of anti-AstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the AstV capsid surface [48] and the immunosuppressing peptides along AstV CP [46,49,50]. Most of AstV vaccine research studies, including our previous study, have been focused on the full-length CP vaccine candidates, which all showed partial unsatisfactory immunity [36,37,51].…”