title: Chimpanzee GB virus C and GB virus A E2 envelope glycoproteins contain a peptide motif that inhibits human immunodeficiency virus type 1 replication in human CD4⁺ T-cells.
abstract: GB virus type C (GBV-C) is a lymphotropic virus that can cause persistent infection in humans. GBV-C is not associated with any disease, but is associated with reduced mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Related viruses have been isolated from chimpanzees (GBV-Ccpz) and from New World primates (GB virus type A, GBV-A). These viruses are also capable of establishing persistent infection. We determined the nucleotide sequence encoding the envelope glycoprotein (E2) of two GBV-Ccpz isolates obtained from the sera of captive chimpanzees. The deduced GBV-Ccpz E2 protein differed from human GBV-C by 31 % at the amino acid level. Similar to human GBV-C E2, expression of GBV-Ccpz E2 in a tet-off human CD4(+) Jurkat T-cell line significantly inhibited the replication of diverse HIV-1 isolates. This anti-HIV-replication effect of GBV-Ccpz E2 protein was reversed by maintaining cells in doxycycline to reduce E2 expression. Previously, we found a 17 aa region within human GBV-C E2 that was sufficient to inhibit HIV-1. Although GBV-Ccpz E2 differed by 3 aa differences in this region, the chimpanzee GBV-C 17mer E2 peptide inhibited HIV-1 replication. Similarly, the GBV-A peptide that aligns with this GBV-C E2 region inhibited HIV-1 replication despite sharing only 5 aa with the human GBV-C E2 sequence. Thus, despite amino acid differences, the peptide region on both the GBV-Ccpz and the GBV-A E2 protein inhibit HIV-1 replication similar to human GBV-C. Consequently, GBV-Ccpz or GBV-A infection of non-human primates may provide an animal model to study GB virus-HIV interactions.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: McLinden
authors.affiliation: Interdisciplinary Program on Molecular and Cellular Biology, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.|Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Klinzman
authors.affiliation: Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Murthy
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kaufman
authors.affiliation: Interdisciplinary Program on Molecular and Cellular Biology, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.|Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nirjal
authors.initials: N
authors.lastname: Bhattarai
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D029405:GB virus A / Q000302:isolation & purification / Q000502:physiology*; D029407:GB virus C / Q000302:isolation & purification / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014762:Viral Interference; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins