the effect of trim5 polymorphisms on the clinical course of hiv-1 infectiontrim5多态性的影响hiv - 1感染的临床过程.pdfVIP

The Effect of Trim5 Polymorphisms on the Clinical Course of HIV-1 Infection ¨ 1,2¤ 1,2¤ 1,2 1,2¤ 1,2,3 Danielle van Manen , Maarten A. N. Rits , Corrine Beugeling , Karel van Dort , Hanneke Schuitemaker , Neeltje A. Kootstra1,2¤* 1 Department of Clinical Viro Immunology, Sanquin Research, Landsteiner Laboratory, University of Amsterdam, Amsterdam, The Netherlands, 2 Center of Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, The Netherlands, 3 Department of Experimental Immunology, Amsterdam Medical Center, Amsterdam, The Netherlands The antiviral factor tripartite interaction motif 5a (Trim5a) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5a is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q) were shown to affect the antiviral activity of Trim5a in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5a that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4) HIV- 1 variants and when a viral load of 104.5 copies per ml plasma was used as an endpoint in survival analys