Tetraspanin CD63 is a regulator of HIV-1 replication

Macrophages and CD4⁺ T-cells are the major reservoirs for HIV-1 infection. CD63 is a tetraspanin transmembrane protein, which has been shown to play an essential role during HIV-1 replication in macrophages. In this study, we further confirm the requirement of CD63 in HIV-1 replication events in primary human CD4⁺ T-cells, dendritic cells, and a CD4⁺ cell line. Most interestingly, we also show the evidences for the co-localization and internalization of CD63 and HIV-1 major receptor CD4 in primary human macrophages and CD4⁺ cell line by confocal microscopy and Co-Immunoprecipitation assay. Analysis revealed that CD63-depleted CD4⁺ T-cells, dendritic cells, and a cell line showed significant decrease in HIV-1 production. Further analysis showed that CD63 down regulation reduced production of the early HIV protein Tat, and affected HIV protein Gag by CD63-Gag interaction. In agreement, CD63 silencing also inhibited production of the late protein p24. Furthermore, we revealed that CD63 silencing has no effect on HIV-1 replication with extensive viral challenge (MOI > 0.2). These findings suggest that CD63 plays a dual-role both in early and late HIV-1 life cycle with a range of HIV-1 infection (MOI < 0.2).     

GAGEC1, a cancer/testis associated antigen family member, is a target of TGF-beta1 in age-related prostatic disease

Transforming growth factor beta (TGF-beta) is a multi-functional cytokine that plays a fundamental role during embryonic development and tissue homeostasis in metazoans. Changes in TGF-beta signalling are implicated in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), two of the most common diseases affecting ageing males. GAGEC1 belongs to the GAGE-related family of cancer/testis associated antigens and in males is expressed only in prostate and testis. Previous reports demonstrate that GAGEC1 is up-regulated in symptomatic BPH and PCa. We demonstrate GAGEC1 up-regulation by TGF-beta1 in primary prostatic stromal and epithelial cells. Our data suggest that disease-associated increases in TGF-beta1 may account for the increase in GAGEC1 expression in BPH and PCa. Given its restricted spatial expression in males, GAGEC1 represents a promising target for therapeutic intervention of BPH and PCa.     

2Apro is a multifunctional protein that regulates the stability, translation and replication of poliovirus RNA

Poliovirus 2A(pro) is required for the inhibition of host cell protein synthesis and efficient viral replication. We investigated the role of 2A(pro) in regulating viral RNA stability, translation and replication in HeLa S10 reactions. The protease activity of 2A(pro) or its polyprotein precursors, 2AB or P2, was required to increase the stability of viral RNA and prolong translation. Since other viral proteins were not required for the observed effects of 2A(pro), it is likely that a cellular protein(s) modified by 2A(pro) mediated these effects on stability and translation. In addition, the protease activity of 2A(pro) stimulated negative-strand initiation by approximately five-fold but had no effect on positive-strand initiation. The 2A(pro) stimulation of negative-strand synthesis was independent of its effect on stability and translation. These findings further extend the previously known functions of protein 2A(pro) to include its role in increasing RNA stability, prolonging translation and stimulating negative-strand synthesis.