Select membrane proteins modulate MNV-1 infection of macrophages and dendritic cells in a cell type-specific manner

Cunha, Juliana Bragazzi; Wobus, Christiane E.

doi:10.1016/j.virusres.2016.06.001

Cited by 13 publications

(6 citation statements)

References 53 publications

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“…Binding of the MNoV-1 particles pretreated with PBS(-)+EDTA (pH 8) to RAW264.7 cells, however, showed no significant difference from those pretreated with DMEM (Left bars in S2A Fig ). RAW264.7 cells are known to express several molecules involved in MNoV adsorption [ 21 ]. In contrast, HEK293T cells genetically expressing CD300lf (HEK293T/CD300lf cells) can adsorb MNoV particles on the cell surface via direct interaction with the CD300lf [ 22 , 23 ].…”

Section: Resultsmentioning

confidence: 99%

Dynamic rotation of the protruding domain enhances the infectivity of norovirus

et al. 2020

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Norovirus is the major cause of epidemic nonbacterial gastroenteritis worldwide. Lack of structural information on infection and replication mechanisms hampers the development of effective vaccines and remedies. Here, using cryo-electron microscopy, we show that the capsid structure of murine noroviruses changes in response to aqueous conditions. By twisting the flexible hinge connecting two domains, the protruding (P) domain reversibly rises off the shell (S) domain in solutions of higher pH, but rests on the S domain in solutions of lower pH. Metal ions help to stabilize the resting conformation in this process. Furthermore, in the resting conformation, the cellular receptor CD300lf is readily accessible, and thus infection efficiency is significantly enhanced. Two similar P domain conformations were also found simultaneously in the human norovirus GII.3 capsid, although the mechanism of the conformational change is not yet clear. These results provide new insights into the mechanisms of non-enveloped norovirus transmission that invades host cells, replicates, and sometimes escapes the hosts immune system, through dramatic environmental changes in the gastrointestinal tract.

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Section: Resultsmentioning

confidence: 99%

Dynamic rotation of the protruding domain enhances the infectivity of norovirus

et al. 2020

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“…Lastly, there may be cell type-specific inhibitors of MNV entry which can interact with I/LnJ CD300LF but not with C57BL/6J CD300LF. A recent study into critical factors for entry of MNV into macrophages and dendritic cells identified several proteins, including CD98 and CD36, that influence attachment and could potentially fulfill such a role ( 46 ). All these three possibilities are plausible, and future studies will investigate these possibilities and attempt to identify this modulatory factor(s).…”

Section: Discussionmentioning

confidence: 99%

CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner

Furlong

Biering

Choi

et al. 2020

J Virol

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Human norovirus is the leading cause of gastroenteritis worldwide, yet basic questions about its life cycle remain unanswered due to an historical lack of robust experimental systems. Recent studies on the closely related murine norovirus (MNV) have identified CD300LF as an indispensable entry factor for MNV. We compared MNV susceptibility of cells from different mouse strains and identified polymorphisms in murine CD300LF, which are critical for its function as an MNV receptor. Bone marrow-derived macrophages (BMDMs) from I/LnJ mice were resistant to infection from multiple MNV strains, which readily infect BMDMs from C57BL/6J mice. The resistance of I/LnJ BMDMs was specific to MNV, since the cells supported infection of other viruses comparably to C57BL/6J BMDMs. Transduction of I/LnJ BMDMs with C57BL/6J CD300LF made the cells permissible to MNV infection, suggesting that the cause of resistance lies in the entry step of MNV infection. In fact, we mapped this phenotype to a 4 amino acid difference at the CC' loop of CD300LF; swapping of these amino acids between C57BL/6J and I/LnJ CD300LF proteins made the mutant C57BL/6J CD300LF functionally impaired and the corresponding mutant of I/LnJ CD300LF functional as an MNV entry factor. Surprisingly, expression of the I/LnJ CD300LF in other cell types made the cells infectible by MNV, even though the I/LnJ allele did not function as an MNV receptor in macrophage-like cells. Correspondingly, I/LnJ CD300LF bound MNV virions in permissive cells but not in non-permissive cells. Collectively, our data suggest the existence of a cell-type-specific modifier of MNV entry. IMPORTANCE MNV is a prevalent model system for studying human norovirus–the leading cause of gastroenteritis worldwide and thus a sizeable public health burden. Elucidating mechanisms underlying susceptibility of host cells to MNV infection can lead to insights on the roles that specific cell types play during norovirus pathogenesis. Here, we show that different alleles of the proteinaceous receptor for MNV, CD300LF, function in a cell type-dependent manner. In contrast to the C57BL/6J allele that functions as an MNV entry factor in all tested cell types, including human cells, I/LnJ CD300LF does not function as an MNV entry factor in macrophage-like cells but does allow MNV entry in other cell types. Together, these observations indicate the existence of cell-type specific modifiers of CD300LF-dependent MNV entry.

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“…Based on previous work demonstrating that OMVs from other commensal bacteria can enter cells and subsequently influence cellular responses ( 43 – 45 ), we examined the ability of OMVs from E. cloacae and B. thetaiotaomicron to enter RAW264.7 cells. In addition, since MNV has been shown to infect macrophages as early as 1 hpi, which is the standard incubation timepoint for MNV infection assays ( 26 , 28 ), we tested if OMVs were capable of entering macrophages within the same time frame. To do this, RAW264.7 macrophages were inoculated with DiO-labeled OMVs, and the cells were visualized after 1 hr of inoculation with fluorescent microscopy.…”

Section: Resultsmentioning

confidence: 99%

Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses

et al. 2022

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Human norovirus is the primary cause of non-bacterial gastroenteritis globally and is the second leading cause of diarrheal deaths in children in developing countries. However, effective therapeutics which prevent or clear norovirus infection are not yet available due to a lack of understanding regarding norovirus pathogenesis. Evidence shows that noroviruses can bind to the surface of commensal bacteria, and the presence of these bacteria alters both acute and persistent murine norovirus infection through the modulation of host immune responses. Interestingly, norovirus-bacterial interactions also affect the bacteria by inducing bacterial stress responses and increasing the production of bacterial extracellular vesicles. Given the established ability of these vesicles to easily cross the intestinal barriers, enter the lamina propria, and modulate host responses, we hypothesized that bacterial extracellular vesicles influence murine norovirus infection through modulation of the antiviral immune response. In this study, we show that murine norovirus can attach to purified bacterial vesicles, facilitating co-inoculation of target cells with both virus and vesicle. Furthermore, we have found that when murine noroviruses and vesicles are used to co-inoculate macrophages, viral infection is reduced compared to virus infection alone. Specifically, co-inoculation with bacterial vesicles results in higher production and release of pro-inflammatory cytokines in response to viral infection. Ultimately, given that murine norovirus infection increases bacterial vesicle production in vivo, these data indicate that bacterial vesicles may serve as a mechanism by which murine norovirus infection is ultimately controlled and limited to a short-term disease.

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Select membrane proteins modulate MNV-1 infection of macrophages and dendritic cells in a cell type-specific manner

Cited by 13 publications

References 53 publications

Dynamic rotation of the protruding domain enhances the infectivity of norovirus

Dynamic rotation of the protruding domain enhances the infectivity of norovirus

CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner

Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses

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