A highly pathogenic simian human immunodeficiency virus with genetic changes in cynomolgus monkey

A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SH IV strain that contains the env gene of pathogenic human immunodeficiency v irus type 1 89,6, CD4(+) lymphocyte depletion was induced within 1 week of the SHIV-C2/1 infection in peripheral blood as well as in various lymphoid organs in all the animals tested, with symptoms of diarrhoea and no increas e in body weight, followed by intense viraemia, Serum antibody against Env protein was detected from 4 weeks after the virus infection, while the anti -Gag antibody response was absent in the SHIV-C2/1-infected animals. In con trast, both anti-Gag and anti-Env antibody responses were present in animal s infected with p-SHIV or the non-pathogenic SHIV-MN. Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid del etion, and in the Nef protein. The pathogenic SHIV-C2/1-monkey model sugges ts that virus-specific pathogenicity in SHIV infection may be associated wi th the absence of anti-Gag antibody responses in animals and may be caused by genetic changes during serum passage in vivo.