Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism. | Dybowski et al. AIDS Research and Therapy 2010 7 41 http content 7 1 41 AIDS RESEARCH AND THERAPY SHORT REPORT Open Access Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism J Nikolaj Dybowski Dominik Heider Daniel Hoffmann Abstract Deep sequencing is able to generate a complete picture of the retroviral quasi-species in a patient. We demonstrate that the unprecedented power of deep sequencing in conjunction with computational data analysis has great potential for clinical diagnostics and basic research. Specifically we analyzed longitudinal deep sequencing data from patients in a study with Vicriviroc a drug that blocks the HIV-1 co-receptor CCR5. Sequences covered the V3-loop of gp120 known to be the main determinant of co-receptor tropism. First we evaluated this data with a computational model for the interpretation of V3-sequences with respect to tropism and we found complete agreement with results from phenotypic assays. Thus the method could be applied in cases where phenotypic assays fail. Second computational analysis led to the discovery of a characteristic pattern in the quasi-species that foreshadows switches of co-receptor tropism. This analysis could help to unravel the mechanism of tropism switches and to predict these switches weeks to months before they can be detected by a phenotypic assay. Findings Human Immunodeficiency Virus 1 HIV-1 enters cells in a complex process involving interactions of viral envelope protein gp120 with the cellular receptor CD4 and a co-receptor typically one of the chemokine receptors CCR5 or CXCR4 1 . According to their co-receptor usage or tropism viruses are classified as R5 interacting with CCR5 or X4 interacting with CXCR4 . Additionally there are dual-tropic R5X4 strains that use both co-receptors for cell entry. Tropism is mainly determined by the sequence of the variable loop 3 V3 of gp120. In initial infection R5 viruses dominate the viral quasi-species
