Construction and infection of a new simian/human immunodeficiency chimeric virus (SHIV) containing the integrase gene of the human immunodeficiency virus type 1 genome and analysis of its adaptation to monkey cells

Abstract Expanding the HIV-1-derived regions in the SHIV genome may help to clarify the viral restriction factors determining the host range. In this study, we constructed a new SHIV having the reverse transcriptase and integrase-encoding regions of HIV-1 in addition to the 3′ half genomic region of HIV-1. This SHIV, termed SHIVrti/3rn, could replicate in a monkey CD4 + T cell line, HSC-F, although its replication in monkey PBMCs was very weak. After SHIVrti/3rn was passaged in HSC-F cells for 26 weeks, it gradually began to replicate in monkey PBMCs. This monkey-cell-adapted virus, termed SHIVrti/3rnP, could replicate in rhesus macaques. The whole genome of SHIVrti/3rnP was sequenced and was found to differ from SHIVrti/3rn at eleven positions. We constructed a series of mutants having some or all of these mutations and investigated their replication kinetics. The mutational analysis revealed that all of the mutations, but mainly the mutations in env , were responsible for the adaptation in HSC-F cells and were enough to replicate in rhesus PBMCs. Of all the SHIVs reported so far that can infect rhesus monkeys in vivo, SHIVrti/3rnP is the one that is genetically the closest to HIV-1.