Early Events in Reovirus Infection Influence Induction of Innate Immune Response

Abad, Andrew T.; Danthi, Pranav

doi:10.1128/jvi.00917-22

Cited by 9 publications

(7 citation statements)

References 69 publications

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“…However, in comparison to T1L, T1L/T3DM2 ISVP uncoats more rapidly or to a greater extent [27] . These differences enable T1L/T3DM2 to initiate infection more expeditiously in host cells [28] .…”

Section: Resultsmentioning

confidence: 99%

Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry

Jiao,

Danthi,

2024

Preprint

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Non-enveloped viruses employ unique entry mechanisms to breach and infect host cells. Understanding these mechanisms is crucial for developing antiviral strategies. Prevailing perspective suggests that non-enveloped viruses release membrane lytic peptides to breach host membranes. However, the precise involvement of the viral capsid in this entry remains elusive. Our study presents direct observations elucidating the dynamically distinctive steps through which metastable reovirus capsids disrupt host lipid membranes as they uncoat into partially hydrophobic intermediate particles. Using both live cells and model membrane systems, our key finding is that reovirus capsids actively deform and permeabilize lipid membranes in a cholesterol-dependent process. Unlike membrane lytic peptides, these metastable viral capsids induce more extensive membrane perturbations, including budding, bridging between adjacent membranes, and complete rupture. Notably, cholesterol enhances subviral particle adsorption, resulting in the formation of pores equivalent to the capsid size . This cholesterol dependence is attributed to the lipid condensing effect, particularly prominent at intermediate cholesterol level . Furthermore, our results reveal a positive correlation between membrane disruption extent and efficiency of viral variants in establishing infection. This study unveils the crucial role of capsid-lipid interaction in non-enveloped virus entry, providing new insights into how cholesterol homeostasis influences virus infection dynamics.

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Section: Resultsmentioning

confidence: 99%

Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry

Jiao,

Danthi,

2024

Preprint

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“…To understand the earliest phenotypic changes in CD8 T cells upon virus exposure, we exposed C57BL/6 mice to reovirus, a naturally occurring prototypic dsRNA virus that causes acute infection and drives immune response ( 25 , 26 ), via intraperitoneal (i.p.) injection and studied CD8 T cell subsets via flow cytometry in the spleen.…”

Section: Resultsmentioning

confidence: 99%

After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism

et al. 2023

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CD8 T cells play a central role in antiviral immunity. Type I interferons are among the earliest responders after virus exposure and can cause extensive reprogramming and antigen-independent bystander activation of CD8 T cells. Although bystander activation of pre-existing memory CD8 T cells is known to play an important role in host defense and immunopathology, its impact on naïve CD8 T cells remains underappreciated. Here we report that exposure to reovirus, both in vitro or in vivo, promotes bystander activation of naïve CD8 T cells within 24 hours and that this distinct subtype of CD8 T cell displays an innate, antiviral, type I interferon sensitized signature. The induction of bystander naïve CD8 T cells is STAT1 dependent and regulated through nicotinamide phosphoribosyl transferase (NAMPT)-mediated enzymatic actions within NAD+ salvage metabolic biosynthesis. These findings identify a novel aspect of CD8 T cell activation following virus infection with implications for human health and physiology.

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“…The expression of interferon-stimulated genes induced by immune-activation signaling of Fc receptors is dampened by DENV binding to LILRB1. Therefore, it is possible that the immune inhibitory signaling induced by reovirus binding to PirB similarly suppresses host innate immune responses elicited by reovirus entry 66 and contributes to establishment of infection. This hypothesis is supported by the exclusive preference of reovirus for PirB and not the paired immune activating receptor PirA (Fig.…”

Section: Discussionmentioning

confidence: 99%

Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus

et al. 2023

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Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen and identified paired immunoglobulin-like receptor B (PirB) as a receptor candidate. Ectopic expression of PirB allowed reovirus binding and infection. PirB extracelluar D3D4 region is required for reovirus attachment and infectivity. Reovirus binds to PirB with nM affinity as determined by single molecule force spectroscopy. Efficient reovirus endocytosis requires PirB signaling motifs. In inoculated mice, PirB is required for maximal replication in the brain and full neuropathogenicity of neurotropic serotype 3 (T3) reovirus. In primary cortical neurons, PirB expression contributes to T3 reovirus infectivity. Thus, PirB is an entry receptor for reovirus and contributes to T3 reovirus replication and pathogenesis in the murine brain.

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Early Events in Reovirus Infection Influence Induction of Innate Immune Response

Abstract: Viruses must infect host cells to replicate, often killing the host cell in the process. However, hosts can activate defenses to limit viral replication and protect the organism.

Cited by 9 publications

References 69 publications

Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry

Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry

After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism

Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus

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