Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity

  title={Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity},
  author={Jun-Young Seo and Rakina Yaneva and Ella R. Hinson and Peter Cresswell},
  pages={1093 - 1097}
Human cytomegalovirus uses a host-encoded antiviral protein to its own advantage. Viperin is an interferon-inducible protein that is directly induced in cells by human cytomegalovirus (HCMV) infection. Why HCMV would induce viperin, which has antiviral activity, is unknown. We show that HCMV-induced viperin disrupts cellular metabolism to enhance the infectious process. Viperin interaction with the viral protein vMIA resulted in viperin relocalization from the endoplasmic reticulum to the… 

Viperin Regulates Cellular Lipid Metabolism during Human Cytomegalovirus Infection

It is shown that all of these metabolic outcomes can be replicated by direct targeting of viperin to mitochondria in the absence of HCMV infection, and that the motif responsible for Fe-S cluster binding by vipersin is essential.

Targeting viperin to the mitochondrion inhibits the thiolase activity of the trifunctional enzyme complex

Results provide biochemical insight into the mechanism by which human cytomegalovirus subverts viperin and provide a biochemical rationale for vipersin's recently discovered role in regulating thermogenesis in adipose tissues.

Viperin Reveals Its True Function.

This review examines the multiple antiviral mechanisms and biological functions attributed to viperin, demonstrated to catalyze the conversion of cytidine triphosphate to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), a previously unknown ribonucleotide.

Human Cytomegalovirus Exploits Interferon-Induced Transmembrane Proteins To Facilitate Morphogenesis of the Virion Assembly Compartment

It is reported that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts and this is the first report of a proviral function of IFITm in DNA virus replication.

Human Viperin Causes Radical SAM-Dependent Elongation of Escherichia coli, Hinting at Its Physiological Role.

It is shown that expression of the human viperin homologue induces a dramatically elongated morphology of the host Escherichia coli cells, indicating the elusive substrate is shared between both bacteria and humans, significantly narrowing the range of potential candidate substrates and providing a convenient bacterial platform from which future studies can occur.

Viperin interaction with mitochondrial antiviral signaling protein (MAVS) limits viperin-mediated inhibition of the interferon response in macrophages

This work identifies the mitochondrial antiviral signalling protein MAVS as a novel viperin interaction partner, most likely in mitochondria associated membranes, and describes a more central, overarching role of vipersin as a negative regulator of the interferon response, an ability that can be regulated by the viperIn-MAVS interaction.

The Interaction Mechanism Between Herpes Simplex Virus 1 Glycoprotein D and Host Antiviral Protein Viperin

GD and viperin interaction was corroborated to significantly inhibit the proliferation of HSV-1 and would open up new avenues toward delineating the function and physiological significance of gD andviperin during HSv-1 replication cycle.

The function and evolution of the restriction factor viperin in primates was not driven by lentiviruses

Findings indicate that Viperin is not a major restriction factor against HIV-1 and other retroviruses, and other viral lineages are likely responsible for the evolutionary signatures of positive selection in viperin among primates.

Ovine viperin inhibits bluetongue virus replication.

Interplay between Human Cytomegalovirus and Intrinsic/Innate Host Responses: A Complex Bidirectional Relationship

This work reviews the viral and cellular partners that mediate early host responses to HCMV, the interaction between structural components of virions and cellular receptors, the reactions of innate immune cells, the numerous mechanisms of viral immunoevasion, and the potential exploitation of events that are associated with early phases of virus-host interplay as a therapeutic strategy.



Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus

  • K. ChinP. Cresswell
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
The identification of a cytoplasmic antiviral protein that is induced by IFNs, by HCMV infection, and by the H CMV envelope protein, glycoprotein B (gB), which is named viperin (for virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible).

Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA

It is shown that vMIA decreases cell size, reduces actin polymerization, and induces cell rounding, which suggests that the cytopathic effect of CMV can be explained by vMia effects on mitochondrial bioenergetics.

A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2.

Human cytomegalovirus (CMV), a herpesvirus that causes congenital disease and opportunistic infections in immunocompromised individuals, encodes functions that facilitate efficient viral propagation by altering host cell behavior and encodes a mitochondria-localized inhibitor of apoptosis, denoted vMIA, capable of suppressing apoptosis induced by diverse stimuli.

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig51

It is concluded that viperin contributes to the antiviral state induced by TLR3 ligation in astrocytes, supporting a role for astroCytes as part of the innate immune response against infection in the CNS.

The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helix

The findings indicate that the amphipathic α-helices of viperin and NS5A are lipid droplet-targeting domains and suggest that vipersin inhibits HCV by localizing to lipid droplets using a domain and mechanism similar to that used by HCV itself.

Cytoskeletal disruption during human cytomegalovirus infection of human lung fibroblasts.

It is demonstrated that rapid cytoskeletal disruption occurs during early periods of HCMV infection and indicates that actin depolymerization facilitates viral infectivity.

Integrin αvβ3 is a coreceptor for human cytomegalovirus

These findings support a model in which EGFR and αvβ3 work together as coreceptors for HCMV entry and signaling, and are fundamental to understanding H CMV pathogenesis and developing treatment strategies targeted to viral receptors.

Human cytomegalovirus UL37 immediate-early regulatory proteins traffic through the secretory apparatus and to mitochondria.

By using confocal microscopy and immunoblotting of fractionated cells, gpUL37 and pUL37x1 were found to co-localize with mitochondria in human cells, which is novel for herpesvirus IE regulatory proteins.

Human cytomegalovirus pUL37x1 induces the release of endoplasmic reticulum calcium stores

It is demonstrated that UL37x1 protein mobilizes Ca2+ from the endoplasmic reticulum into the cytosol, which likely has multiple consequences, including induction of the unfolded protein response, modulation of mitochondrial function, induction of mitochondrial fission, and protection against apoptotic stimuli.