scholarly journals Novel host restriction factors implicated in HIV-1 replication

2018 ◽  
Vol 99 (4) ◽  
pp. 435-446 ◽  
Author(s):  
Dibya Ghimire ◽  
Madhu Rai ◽  
Ritu Gaur
Keyword(s):  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Novel Host ◽  
Hiv 1

Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic Interplay Involving All Phases of the Viral Life Cycle

2018 ◽  
Vol 16 (3) ◽  
pp. 184-207 ◽  
Author(s):  
Vanessa D`Urbano ◽  
Elisa De Crignis ◽  
Maria Carla Re
Keyword(s):  
Mammalian Cells ◽  
Viral Evolution ◽  
Type I ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Immunodeficiency Virus ◽  
Lentiviral Infection ◽  
Specific Proteins ◽  
Hiv 1

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus. The identification and characterization of RFs have provided unique insights into the molecular biology of HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection. The presence of RFs drove viral evolution, forcing the virus to develop specific proteins to counteract their activity. The knowledge of the mechanisms that prevent viral infection and their viral counterparts may offer new insights to improve current antiviral strategies. This review provides an overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expression as well as their impact on viral replication and the clinical course of the disease.

scholarly journals Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV

2020 ◽  
Vol 16 (1) ◽  
pp. e1008268 ◽  
Author(s):  
Nenavath Gopal Naik ◽  
Thomas Hong Nguyen ◽  
Lauren Roberts ◽  
Luke Todd Fischer ◽  
Katherine Glickman ◽  
...  
Keyword(s):  
Lytic Cycle ◽  
Restriction Factors ◽  
Sirna Screen ◽  
Kshv Infection ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Epigenetic Factor ◽  
Novel Host

scholarly journals The Evolutionary Histories of Antiretroviral Proteins SERINC3 and SERINC5 Do Not Support an Evolutionary Arms Race in Primates

2016 ◽  
Vol 90 (18) ◽  
pp. 8085-8089 ◽  
Author(s):  
Ben Murrell ◽  
Thomas Vollbrecht ◽  
John Guatelli ◽  
Joel O. Wertheim
Keyword(s):  
Viral Infections ◽  
Arms Race ◽  
Restriction Factor ◽  
Restriction Factors ◽  
Arms Races ◽  
Host Restriction ◽  
Host Restriction Factor ◽  
Novel Host ◽  
Evolutionary Arms Race ◽  
Hiv 1

ABSTRACTMolecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses and their antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-α, SAMHD1, and BST-2. Host restriction factors have experienced some of the most intense and pervasive adaptive evolution documented in primates. Recently, two novel host factors, SERINC3 and SERINC5, were identified as the targets of HIV-1 Nef, a protein crucial for the optimal infectivity of virus particles. Here, we compared the evolutionary fingerprints of SERINC3 and SERINC5 to those of other primate restriction factors and to a set of other genes with diverse functions. SERINC genes evolved in a manner distinct from the canonical arms race dynamics seen in the other restriction factors. Despite their antiviral activity against HIV-1 and other retroviruses, SERINC3 and SERINC5 have a relatively uneventful evolutionary history in primates.IMPORTANCERestriction factors are host proteins that block viral infection and replication. Many viruses, like HIV-1 and related retroviruses, evolved accessory proteins to counteract these restriction factors. The importance of these interactions is evidenced by the intense adaptive selection pressures that dominate the evolutionary histories of both the host and viral genes involved in this so-called arms race. The dynamics of these arms races can point to mechanisms by which these viral infections can be prevented. Two human genes, SERINC3 and SERINC5, were recently identified as targets of an HIV-1 accessory protein important for viral infectivity. Unexpectedly, we found that these SERINC genes, unlike other host restriction factor genes, show no evidence of a recent evolutionary arms race with viral pathogens.

scholarly journals Specific Deubiquitinating Enzymes Promote Host Restriction Factors Against HIV/SIV Viruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenying Gao ◽  
Yajuan Rui ◽  
Guangquan Li ◽  
Chenyang Zhai ◽  
Jiaming Su ◽  
...  
Keyword(s):  
Viral Replication ◽  
Ectopic Expression ◽  
Specific Inhibitor ◽  
Restriction Factors ◽  
Deubiquitinating Enzymes ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Virion Infectivity Factor ◽  
Specific Protease ◽  
Hiv 1

Hijacking host ubiquitin pathways is essential for the replication of diverse viruses. However, the role of deubiquitinating enzymes (DUBs) in the interplay between viruses and the host is poorly characterized. Here, we demonstrate that specific DUBs are potent inhibitors of viral proteins from HIVs/simian immunodeficiency viruses (SIVs) that are involved in viral evasion of host restriction factors and viral replication. In particular, we discovered that T cell-functioning ubiquitin-specific protease 8 (USP8) is a potent and specific inhibitor of HIV-1 virion infectivity factor (Vif)-mediated apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)G (A3G) degradation. Ectopic expression of USP8 inhibited Vif-induced A3G degradation and suppressed wild-type HIV-1 infectivity even in the presence of Vif. In addition, specific DUBs repressed Vpr-, Vpu-, and Vpx-triggered host restriction factor degradation. Our study has revealed a previously unrecognized interplay between the host’s DUBs and viral replication. Enhancing the antiviral activity of DUBs therefore represents an attractive strategy against HIVs/SIVs.

scholarly journals Dodging the Host Interferon-Stimulated Gene Mediated Innate Immunity by HIV-1: A Brief Update on Intrinsic Mechanisms and Counter-Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Kumaraswami Chintala ◽  
Krishnaveni Mohareer ◽  
Sharmistha Banerjee
Keyword(s):  
Innate Immunity ◽  
Life Cycle ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Innate Immune Responses ◽  
Restriction Factors ◽  
Host Restriction ◽  
Interferon Stimulated Genes ◽  
Host Restriction Factors ◽  
Hiv 1

Host restriction factors affect different phases of a viral life cycle, contributing to innate immunity as the first line of defense against viruses, including HIV-1. These restriction factors are constitutively expressed, but triggered upon infection by interferons. Both pre-integration and post-integration events of the HIV-1 life cycle appear to play distinct roles in the induction of interferon-stimulated genes (ISGs), many of which encode antiviral restriction factors. However, HIV-1 counteracts the mechanisms mediated by these restriction factors through its encoded components. Here, we review the recent findings of pathways that lead to the induction of ISGs, and the mechanisms employed by the restriction factors such as IFITMs, APOBEC3s, MX2, and ISG15 in preventing HIV-1 replication. We also reflect on the current understanding of the counter-mechanisms employed by HIV-1 to evade innate immune responses and overcome host restriction factors. Overall, this mini-review provides recent insights into the HIV-1-host cross talk bridging the understanding between intracellular immunity and research avenues in the field of therapeutic interventions against HIV-1.

scholarly journals O5 The expression profile of host restriction factors in different cohorts of HIV-1-infected patients

2017 ◽  
Vol 3 ◽  
pp. 2
Author(s):  
C. Van Hecke ◽  
E. Malatinkova ◽  
W. De Spiegelaere ◽  
M. Sips ◽  
K. Vervisch ◽  
...  
Keyword(s):  
Expression Profile ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Hiv 1

Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors

10.1038/nm910 ◽  
2003 ◽  
Vol 9 (9) ◽  
pp. 1138-1143 ◽  
Author(s):  
Greg J Towers ◽  
Theodora Hatziioannou ◽  
Simone Cowan ◽  
Stephen P Goff ◽  
Jeremy Luban ◽  
...  
Keyword(s):  
Cyclophilin A ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Hiv 1

scholarly journals TRIM5 and the Regulation of HIV-1 Infectivity

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jeremy Luban
Keyword(s):  
Innate Immune ◽  
Target Cells ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Innate Immune Signaling ◽  
Ubiquitin Ligase Activity ◽  
Species Specific ◽  
Anti Hiv ◽  
Hiv 1

The past ten years have seen an explosion of information concerning host restriction factors that inhibit the replication of HIV-1 and other retroviruses. Among these factors is TRIM5, an innate immune signaling molecule that recognizes the capsid lattice as soon as the retrovirion core is released into the cytoplasm of otherwise susceptible target cells. Recognition of the capsid lattice has several consequences that include multimerization of TRIM5 into a complementary lattice, premature uncoating of the virion core, and activation of TRIM5 E3 ubiquitin ligase activity. Unattached, K63-linked ubiquitin chains are generated that activate the TAK1 kinase complex and downstream inflammatory mediators. Polymorphisms in the capsid recognition domain of TRIM5 explain the observed species-specific differences among orthologues and the relatively weak anti-HIV-1 activity of human TRIM5. Better understanding of the complex interaction between TRIM5 and the retrovirus capsid lattice may someday lead to exploitation of this interaction for the development of potent HIV-1 inhibitors.

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