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.

Interacción entre el virus de la inmunodeficiencia humana y el virus GB tipo-C durante el estado de co-infección

“…Análisis más detallados, han demostrado que la región de la proteína correspondiente a los residuos aminoacídicos del 152 a 236 de la proteína son suficientes para inhibir la replicación del VIH. Adicionalmente, se reportó inhibición cuando se expresó la región con los aminoácidos entre 152-181, región en la que se encuentran cuatro sitios de fosforilación, los cuales serían importantes para la actividad inmunomoduladora, lo que sugiere la existencia de mecanismos adicionales que median la inhibición del VIH 50,51 . Estos resultados sugieren que todos los genotipos del GBV-C son capaces de inhibir la replicación del VIH, y que el posible mecanismo se relaciona con la modulación en la producción de la quimioquina SDF-1, quimioquina con potencial para competir por el co-receptor CXCR4, para lo cual se ha propuesto que es capaz de afectar pasos post-entrada, similar a lo reportado para MIP1-α 52 .…”

RNA interference effectively degrades mRNA and inhibits protein expression of GBV-C E2 gene in Huh7 cells

“…The protein(s) of GBV-C that lead to HIV inhibition are not defined. Xiang's studies showed that the GBV-C NS5A could inhibit HIV-1 replication [18][19][20]. The effect of GBV-C E2 protein remains to be resolved in HIV-1 co-infection.…”

The GB Virus C (GBV-C) NS3 Serine Protease Inhibits HIV-1 Replication in a CD4+ T Lymphocyte Cell Line without Decreasing HIV Receptor Expression

“…GBV-C infection of PBMCs and CD4+ T cells increases secretion of CCR5 ligand chemokines and decreases CCR5 expression by 50% compared with mock-infected PBMCs [30], [31]. Two GBV-C proteins, NS5A [32]–[35] and the envelope glycoprotein E2 [36]–[40], inhibit HIV replication in CD4+ Jurkat cells by either decreasing HIV receptor expression (NS5A) or blocking HIV attachment and entry (E2). NS5A expressed in CD4+ Jurkat T cells inhibits HIV replication by decreasing expression of CD4 [35] and CXCR4 [32]–[34].…”

“…Two GBV-C proteins, NS5A [32]–[35] and the envelope glycoprotein E2 [36]–[40], inhibit HIV replication in CD4+ Jurkat cells by either decreasing HIV receptor expression (NS5A) or blocking HIV attachment and entry (E2). NS5A expressed in CD4+ Jurkat T cells inhibits HIV replication by decreasing expression of CD4 [35] and CXCR4 [32]–[34]. This effect is mediated in part by enhanced secretion of the CXCR4 ligand chemokine SDF-1 [33], [34].…”