Molecular cloning and cell-specific growth characterization of polymorphicvariants of type D serogroup 2 Simian retroviruses

Simian retroviruses (SRVs), the etiological agent of a spontaneous Simian a cquired immunodeficiency syndrome, endemically infects large percentages of Asian macaques housed in biomedical research colonies and severely comprom ises the effective use of these species as a viable research animal. We rec ently described the molecular cloning of a serogroup 2 SRV, D2/RHE/OR, whic h causes mild immunosuppression in rhesus macaques. A restriction site vari ant, D2/RHE/OR/V1, has also been recovered from severely ill animals endemi cally infected with D2/RHE/OR. We now report the complete nucleotide sequen ces of D2/RHE/OR and D2/RHE/OR/V1. Both infectious molecular clones retain the genetic structure typical of type D SRVs (5' LTR-gag-prt-pol-env-3'LTR) and encode identically sized 8105-bp proviruses. D2/RHE/OR and D2/RHE/OR/V 1 are 99.3% similar at the amino acid level, exhibiting only 17 residue dif ferences, of which 10 are located in the envelope glycoproteins. The molecu lar clones and reciprocal chimeric viruses were used to assess the contribu tion of different genetic domains to virus infectivity in a T cell infectio n assay. These experiments indicate that D2/RHE/OR has a reduced ability to infect specific T cell lines, especially Hut-78 and MT-4 cells, and that t he envelope gene is not the sole determinant of in vitro tropism. (C) 1999 Academic Press.