GB virus C: cellular interactions, HIV inhibition and natural history

نویسندگان

  • Emma Louise Mohr
  • Emma Mohr
چکیده

GB virus C (GBV-C) is a nonpathogenic lymphotropic virus that replicates in B and T lymphocytes. Infection with GBV-C is documented worldwide and is common: between 1% and 5% of healthy blood donors are viremic at the time of donation. Antibodies to GBV-C proteins are not usually detected during viremia, and antibodies to the GBV-C envelope glycoprotein E2 develop following the clearance of viremia. Although GBV-C viremia may persist for decades, viremia usually clears within 2 years following infection in the majority of individuals infected by blood transfusion. A chimpanzee variant of GBV-C, designated GBV-Ccpz, is found in captive and noncaptive chimpanzees and its prevalence and natural history are uncharacterized. HIV-infected individuals who are co-infected with GBV-C survive longer than those without GBV-C. GBV-C infection of PBMCs inhibits the replication of HIV isolates and one of the mechanisms for this is the downregulation of HIV coreceptors and secretion of the coreceptor ligands. Additional mechanisms of HIV inhibition by GBV-C are examined in this dissertation. The GBV-C envelope glycoprotein E2 contributes directly to the inhibition of HIV infection. Incubation of recombinant E2 with PBMCs at 4°C prior to HIV infection results in a decrease in HIV replication, and only HIV enveloped pseudoparticle transduction, not VSV-G enveloped pseudoparticle transduction, is inhibited by GBV-C E2. This suggests that GBV-C E2 inhibits HIV infection at an entry step when the HIV envelope proteins interact with cellular receptors and membranes. How GBV-C E2 interacts with cellular surfaces and which cellular proteins are utilized for GBV-C binding and entry are unknown. Here, we characterize GBV-C E2 binding to human PBMCs, murine cells, and multiple transformed cell lines to identify the PBMC subset to which E2 binds and to identify candidate cellular receptors involved in GBV-C binding and entry. Understanding how GBV-C E2 interacts with cellular surfaces is critical to determining how it inhibits HIV entry.

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تاریخ انتشار 2016