tailieunhanh - Báo cáo y học: " Variability in a dominant block to SIV early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death"

Variability in a dominant block to SIV early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death | Rogers et al. Virology Journal 2010 7 79 http content 7 1 79 VIROLOGY JOURNAL RESEARCH Open Access Variability in a dominant block to SIV early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death Thomas F Rogers So-Yon Lim TJ Sundsvold Tiffany Chan Ariel Hsu and Norman L Letvin Abstract While it has long been appreciated that there is considerable variability in host containment of HIV SIV replication the determinants of that variability are not fully understood. Previous studies demonstrated that the degree of permissivity of a macaque s peripheral blood mononuclear cells PBMC for infection with simian immunodeficiency virus SIV in vitro predicted that animal s peak plasma virus RNA levels following SIV infection in vivo. The present study was conducted to define the mechanisms underlying the variable intrinsic susceptibility of rhesus monkey PBMC to SIVsmE660 infection. In a cohort of 15 unrelated Indian-origin rhesus monkeys infectability of PBMC of individual animals with SIVsmE660 as defined by tissue culture infectious dose TCID50 varied by more than 3 logs and was a stable phenotype over time. Susceptibility of a monkey s PBMC to wild type SIVsmE660 infection correlated with the susceptibility of that monkey s PBMC to infection with VSV-G pseudotyped SIVsm543-GFP. Moreover the permissivity of an individual monkey s PBMC for infection with this construct correlated with the permissivity of a B-lymphoblastoid cell line B-LCL generated from PBMC of the same animal. We found that the degree of intrinsic resistance of monkey B-LCL correlated with the copy number of early reverse transcription ERT SIV DNA. The resistance of monkey B-LCL to SIVsmE660 replication could be abrogated by preincubation of cells with the SIV virus-like particles VLPs and SIV resistance phenotype could be transferred to a SIV susceptible B-LCL through cell fusion. Finally we observed a positive correlation between .