title: Expression of GB virus C NS5A protein from genotypes 1, 2, 3 and 5 and a 30 aa NS5A fragment inhibit human immunodeficiency virus type 1 replication in a CD4+ T-lymphocyte cell line.
abstract: GB virus type C (GBV-C) is a common human flavivirus that has been associated with prolonged survival in HIV-positive individuals in several, though not all, epidemiological studies. There are five distinct GBV-C genotypes that are geographically localized, and it has been speculated that GBV-C genotypic differences may explain variable outcomes observed in different clinical studies. Expression of an 85 aa fragment of the GBV-C NS5A phosphoprotein (genotype 2) in a CD4+ T cell line (Jurkat) resulted in inhibition of HIV replication, mediated in part by decreased surface expression of the HIV coreceptor CXCR4 and upregulation of SDF-1. We expressed the NS5A protein from genotypes 1, 2, 3 and 5 in Jurkat cells, and demonstrated that all genotypes inhibited HIV replication. Further deletion mapping demonstrated that expression of a 30 aa fragment resulted in decreased CXCR4 surface expression, upregulation of SDF-1 and inhibition of HIV replication.
authors.affiliation: Iowa City VA Medical Center and the University of Iowa, Iowa City, IA 52246, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Iowa City VA Medical Center and the University of Iowa, Iowa City, IA 52246, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: McLinden
authors.affiliation: Iowa City VA Medical Center and the University of Iowa, Iowa City, IA 52246, USA.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
authors.affiliation: Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, South Africa.
authors.forename: M Aslam
authors.initials: MA
authors.lastname: Sathar
authors.affiliation: Iowa City VA Medical Center and the University of Iowa, Iowa City, IA 52246, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000595:Amino Acid Sequence; D054377:Chemokine CXCL12 / Q000378:metabolism; D015536:Down-Regulation; D029407:GB virus C / Q000737:chemistry*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D010750:Phosphoproteins; D019718:Receptors, CXCR4; D017361:Viral Nonstructural Proteins