Báo cáo y học: " Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: " Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies. | Richards etal. Retrovirology 2010 7 48 http content 7 1 48 gtr RETR0VIR0L0GY SHORT REPORT Open Access Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies Kathryn H Richards 1 4 Marlén MI Aasa-Chapman 2 Áine McKnight3 and Paul R Clapham 1 Abstract HIV-1 R5 viruses vary widely in their capacity to infect primary macrophages. R5 macrophage-tropism is associated with an increased envelope CD4 affinity that partly results from an increased exposure of CD4 contact residues on gp120 and allows the use of low levels of CD4 for infection. The selective pressures in vivo that modulate R5 macrophage-tropism are not understood. It is possible that different R5 variants adapt for replication in either T-cells high CD4 or in macrophages low CD4 . However other selective pressures in vivo . neutralizing antibodies may also impact R5 tropism. Here we measured macrophage infectivity conferred by gp120 sequences amplified sequentially from subjects in London followed from the acute stage of infection. We report wide variation in the capacity of these envelopes to confer macrophage infection in the complete absence of both autologous and heterologous neutralizing antibodies. Our data show that the variation in macrophage tropism observed at early times cannot have been influenced by neutralizing antibodies. Findings HIV-1 R5 viruses that use CCR5 R5 as a coreceptor are preferentially transmitted. Although such viruses are often termed macrophage-tropic or M-tropic 1 we and others have described a wide variation in their capacity to infect primary macrophages 2-7 . In particular we showed that R5 envelopes amplified from brain tissue of subjects with neurological complications were frequently highly macrophage-tropic mac-tropic while many of those from immune tissue blood and semen infected macrophages inefficiently 3 . The capacity of R5 envelopes to confer infection of macrophages correlated with their

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