In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts

Author summary CD8+ T-cell responses exert considerable control over replication of HIV and select for viral escape mutations. Recent studies have suggested that these major histocompatibility complex class I (MHC-I)-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Other studies have shown that some of these escape mutations can revert after passage to MHC-I-disparate hosts. In an attempt to reconcile these apparently conflicting results, we serially passaged a virus isolate through MHC-I-mismatched hosts in the macaque AIDS model of simian immunodeficiency virus (SIV) infection. Here we show an increase in the in vivo virulence of an MHC-I-adapted virus despite a reduction in in vitro viral replication capacity. Only a few of the selected escape mutations reverted after transmission to MHC-I-disparate recipients. Results clearly showed that MHC-I-adapted SIVs that have been serially-transmitted through MHC-I-mismatched hosts can have higher in vivo virulence in MHC-I-matched hosts despite their lower in vitro viral fitness. This study suggests that HIVs may become less sensitive to CD8+ T cell responses and could have increased in vivo virulence by adaptation to MHC-I in human populations.See it on Scoop.it, via Viruses and Bioinformatics from Virology.uvic.ca
In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts
Source: Viral Bioinformatics