GB virus type C interactions with HIV: the role of envelope glycoproteins.
GB virus C/hepatitis G virus (GBV-C/HGV) is the most closely related human virus to hepatitis C virus (HCV). GBV-C is lymphotropic and not associated with any known disease, although it is associated with improved survival in HIV-infected individuals. In peripheral blood mononuclear cells, GBV-C induces the release of soluble ligands for HIV entry receptors (RANTES, MIP-1a, MIP-1b and SDF-1), suggesting that GBV-C may interact with lymphocytes to induce a chemokine and/or cytokine milieu that is inhibitory to HIV infection. Expression of GBV-C envelope glycoprotein E2 in CD4+ T cells or addition of recombinant E2 to CD4 cells recapitulates the HIV inhibition seen with GBV-C infection. Like HCV E2, GBV-C E2 is predicted to be post-translationally processed in the endoplasmic reticulum and is involved with cell binding. The C-termini of GBV-C E1 and E2 proteins contain predicted transmembrane domains sharing features with HCV TM domains. To date, cellular receptor(s) for GBV-C E2 have not been identified. GBV-C E2-mediated HIV inhibition is dose-dependent and HIV replication is blocked at the binding and/or entry step. In addition, a putative GBV-C E2 fusion peptide interferes with HIV gp41 peptide oligomerization required for HIV-1 fusion, further suggesting that GBV-C E2 may inhibit HIV entry. Additional work is needed to identify the GBV-C E2 cellular receptor, characterize GBV-C E2 domains responsible for HIV inhibition, and to examine GBV-C E2-mediated fusion in the context of the entire envelope protein or viral-particles. Understanding the mechanisms of action may identify novel approaches to HIV therapy.
Mohr
Emma L
EL
Department of Internal Medicine and the Interdisciplinary Program on Molecular and Cellular Biology, The University of Iowa, Iowa City, IA 52242, USA.
Stapleton
Jack T
JT
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018178:Flaviviridae Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology; D029407:GB virus C / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000401:mortality / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000453:epidemiology / Q000821:virology; D006801:Humans; D014759:Viral Envelope Proteins / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D014759:Viral Envelope Proteins; C107619:glycoprotein E2, GB virus C