Biology subjects

Reynoso, G. V.

Publications and source records attributed to Reynoso, G. V..

3 recordsLinked to original sources

bioRxiv2022

Zika virus spreads through infection of lymph node-resident macrophages

Zika virus (ZIKV) is an arthopod-vectored flavivirus that disseminates from the infection site into peripheral tissues, where it can elicit virus-induced pathology. To move through the body, ZIKV is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, multiple distinct steps during viral spread culminate in peripheral tissue infection, and the timing and mechanisms underlying mobile immune cell shuttling of virus remain unclear. To understand the very early steps in ZIKV dissemination from the skin, we kinetically and spatially mapped ZIKV-infected lymph nodes (LNs), an intermediary stop en route to the blood. Contrary to dogma, migratory immune cells were not required for large quantities of virus to reach the LN or blood. Instead, ZIKV rapidly infected a subset of immobile macrophages in the LN, which shed virus through the lymphatic pathway into the blood. Importantly, infection of LN macrophages alone was sufficient to initiate viremia. Together, our studies indicate that sessile macrophages that live and die in the LN contribute to initial ZIKV spread to the blood. These data build a more complete picture of ZIKV movement through the body and identify an alternate anatomical site for potential antiviral intervention. HighlightsO_LIZIKV infects and replicates in distinct LN macrophage populations C_LIO_LILN macrophage infection results in infectious virus in the blood C_LIO_LIVirus reaches the blood in the absence of DC migration or monocyte infection C_LIO_LINodal macrophage infection does not sustain viremia or induce morbidity C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=74 HEIGHT=200 SRC="FIGDIR/small/508424v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@121bc33org.highwire.dtl.DTLVardef@1caf24borg.highwire.dtl.DTLVardef@e94a08org.highwire.dtl.DTLVardef@1fb6f62_HPS_FORMAT_FIGEXP M_FIG Caption: ZIKV infects lymph node macrophages, which shed infectious virus into the lymph and then blood. C_FIG

microbiology↗

bioRxiv2022

The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell-infected cell contacts

The success of poxviruses as pathogens depends upon their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation. Here, we demonstrate by quantitative immunofluorescence imaging that C15 also limits contact between natural killer (NK) cells and infected cells in vivo. This corresponds to an inhibition in the number of total and degranulating NK cells, ex vivo and in vitro, with no detectable impact on NK cell cytokine production nor the transcription of factors related to NK cell recruitment or activation. Thus, in addition to its previously identified capacity to antagonize CD4 T cell activation, C15 inhibits NK cell cytolytic function, which results in increased viral replication and dissemination in vivo. This work builds on a body of literature demonstrating the importance of early restriction of virus within the draining lymph node. summaryPoxvirus B22 family proteins are important virulence factors known to inhibit T cell functions. Peauroi et al. identify a novel function of the ectromelia virus homolog, C15, which inhibits NK cell-target contact and cytolytic function to facilitate early viral spread. (Provide a short, [~]40-word summary statement for the online JEM table of contents and alerts. This summary should describe the context and significance of the findings for a general readership; it should be written in the present tense and refer to the work in the third person.)

immunology↗

bioRxiv2021

MARCO+ lymphatic endothelial cells sequester arboviruses to limit viremia and viral dissemination

While viremia in the vertebrate host is a major determinant of arboviral reservoir competency, transmission efficiency, and disease severity, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, alphavirus particles are cleared from the circulation by MARCO-expressing Kupffer cells in the liver, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the dLN and liver is an important host defense mechanism as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease is more severe. These findings uncover a previously unrecognized arbovirus scavenging role for LECs and improve our mechanistic understanding of viremia control during arboviral infections.

immunology↗