The Construction and Evaluation of SIV/HIV Chimeras That Express the Envelope of European HIV Type 1 Isolates

Abstract

The molecular construction of SIV/HIV-1 chimeric viruses (or SHIVs), provides a means of infecting macaques with immunodeficiency viruses that express the envelope protein of HIV-1. However, to date, most SHIVs produced express the envelope of isolates of HIV-1 that have been passaged repeatedly in T cell lines. We have taken SHIV-4 and replaced an NheI-AvrII fragment that encompasses the gp120 region and the extracellular portion of gp41 with the equivalent region of two European isolates of HIV-1 (ACH320.3.1 and HIV-1 _Han-2). Neither of these viruses had been passaged in T cell lines for prolonged periods prior to molecular cloning. Virus stocks were prepared of both SHIV constructs. In vitro, the relative ability of each clone to replicate in four T cell lines mirrored closely the pattern observed with the parental virus donating the envelope sequences. In vivo, only one of the chimeric viruses was infectious in cynomolgus macaques and its recovery was transient. The factors that affect the replication of SHIVs in vitro and in vivo are discussed.