Sequence polymorphisms in the reovirus σ1 attachment protein modulate encapsidation efficiency and replication in mice.

Unlabelled: Many functions of viral attachment proteins are established, but less is known about the biological importance of viral attachment protein encapsidation efficiency. The mammalian orthoreovirus (reovirus) σ1 attachment protein forms filamentous trimers that incorporate into pentamers of the λ2 capsid protein. Reovirus strains vary in the efficiency of σ1 encapsidation onto progeny virions, which influences viral stability during entry into cells and the efficacy of tumor cell lysis.

Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid.

Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide.

Ins and Outs of Reovirus: Vesicular Trafficking in Viral Entry and Egress.

Cell entry and egress are essential steps in the viral life cycle that govern pathogenesis and spread. Mammalian orthoreoviruses (reoviruses) are nonenveloped viruses implicated in human disease that serve as tractable models for studies of pathogen-host interactions. In this review we discuss the function of intracellular vesicular transport systems in reovirus entry, trafficking, and egress and comment on shared themes for diverse viruses.

Norovirus infection causes acute self-resolving diarrhea in wild-type neonatal mice.

Human noroviruses are the leading cause of severe childhood diarrhea worldwide, yet we know little about their pathogenic mechanisms. Murine noroviruses cause diarrhea in interferon-deficient adult mice but these hosts also develop systemic pathology and lethality, reducing confidence in the translatability of findings to human norovirus disease. Herein we report that a murine norovirus causes self-resolving diarrhea in the absence of systemic disease in wild-type neonatal mice, thus mirroring the key features of human norovirus disease and representing a norovirus small animal disease model in wild-type mice.

Diverse Mechanisms Underlie Enhancement of Enteric Viruses by the Mammalian Intestinal Microbiota.

Over the past two decades, there has been tremendous progress in understanding the impact of the intestinal microbiota on mammalian metabolism, physiology, and immune development and function. There has also been substantial advancement in elucidating the interplay between commensal and pathogenic bacteria. Relatively more recently, researchers have begun to investigate the effect of the intestinal microbiota on viral pathogenesis.

The major targets of acute norovirus infection are immune cells in the gut-associated lymphoid tissue.

Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year . Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism.

Norovirus mechanisms of immune antagonism.

Noroviruses are a leading cause of gastroenteritis outbreaks globally. Several lines of evidence indicate that noroviruses can antagonize or evade host immune responses, including the absence of long-lasting immunity elicited during a primary norovirus exposure and the ability of noroviruses to establish prolonged infections that are associated with protracted viral shedding. Specific norovirus proteins possessing immune antagonist activity have been described in recent years although mechanistic insight in most cases is limited.

A gammaherpesvirus Bcl-2 ortholog blocks B cell receptor-mediated apoptosis and promotes the survival of developing B cells in vivo.

Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) establish lifelong latency in their hosts and are associated with the development of several types of malignancies, including a subset of B cell lymphomas. These viruses are thought to co-opt the process of B cell differentiation to latently infect a fraction of circulating memory B cells, resulting in the establishment of a stable latency setpoint. However, little is known about how this infected memory B cell compartment is maintained throughout the life of the host.