The HIV-1 reservoir in distinct V? subsets of CD4 T cells: evidence for a putative superantigen

Abstract

Human immunodeficiency virus-1 (HIV-1) replicates more efficiently in T cells expressing T-cell receptors using certain V beta genes, V beta 12 in particular. This V beta specificity was consistent with an HIV-1-associated superantigen. In addition, T cell-depleted peripheral blood mononuclear cells from HIV-positive donors potently stimulated V beta 12 cell lines to proliferate in culture, but not control B beta 6.7a cell lines, thus indicating the presence of a V beta-selective mitogen. The targeted V beta subsets were not deleted. It was therefore possible that these subsets might represent a viral reservoir in vivo. Viral load was assessed by quantitative polymerase chain reaction (with HIV-1 gag primers) and with an infectivity assay to measure competent virus. It was shown that the tiny V beta 12 subset (1-2% of T cells) has a higher viral load than other V beta subsets in about 65% of infected individuals. Selective HIV-1 replication in V beta 12 cells was also observed 6-9 days after in vitro infection of peripheral blood T cells from several normal HIV-1-negative donors. In summary, a superantigen-like activity appears to promote V beta-selective HIV-1 replication in vitro and in vivo in patients infected with HIV-1. New therapeutic approaches are suggested based on these findings.

Viral Superantigens

“…İnsanda ciddi enfeksiyonlara yol açan çeşitli virusların varlığına rağmen, patogenezinde, SAg özelliği gösteren proteinlerin tanımlandığı virus sayısı görece olarak azdır. Bugüne dek SAg kodladığı belirlenen viruslar; MMTV (1991), kuduz virusu (1992), EBV (1996), insan endojen retrovirusu (1997), HIV (1997) ve Ebola virus (2011) olarak sıralanabilir [8][9][10][11][12][13][14] .…”

“…Nef'in sebep olduğu T hücre aktivasyonunun, SAg özelliğine bağlı olabileceği düşünülmektedir. Nef, enfeksiyonun erken döneminde, M-tropik HIV ile enfekte makrofajlardan salınmakta ve seçici olarak Vβ5, 8, 12-18 TCR taşıyan CD4 + T hücrelerini aktive etmektedir 12,44 . Böylece dinlenme halindeki CD4 + T hücrelerinin masif aktivasyonu ve proliferasyonu gerçekleşmekte; yani virus, replike olabilmek için kendisine bol miktarda aktive T hücre havuzu oluşmaktadır 45 .…”

Rapid and sensitive detection of cell-associated HIV-1 in latently infected cell lines and in patient cells using sodium-n-butyrate induction and RT-PCR

“…Progression of disease in human immunodeficiency virus (HIV) infected subjects is commonly measured indirectly using surrogate markers, such as CD4 cell count, ␤2-microglobulin or interferon levels, often supplemented with direct approaches measuring the viral load [Fang et al, 1995;Posnett et al, 1995]. Many different assays have been developed to determine the viral load qualitatively and quantitatively in serum/ plasma and/or to monitor the effectiveness of antiviral drugs by measuring either viral RNA or antigen levels [Piatak et al, 1993;Ferre et al, 1993;Gupta et al, 1993;Urdea et al, 1993;Carton et al 1994;Fiscus et al, 1995;Katzenstein et al, 1995;Dickover et al, 1996].…”