CD4+ lymphocytopenia in acute infection of Asian macaques by a vaginally transmissible subtype-C, CCR5-tropic simian/human immunodeficiency virus (SHIV)

Abstract

An R5-tropic SHIVCHN19P4 was previously generated using a primary HIV-1 subtype-C envelope. We have further characterized this SHIV in two species of macaques. To determine whether this isolate is transmissible vaginally, female pigtailed macaques were inoculated with 2x103 TCID50 of SHIVCHN19P4 by the vaginal route. Animals became infected with a high peak plasma viremia (>107 viral copies/mL) and rapid seroconversion. The viremia was accompanied by CD4+ lymphocytopenia in the gut lamina propria lymphocyte (LPL) population. Comparable CD4+ T-cell loss was not seen in peripheral blood and colonic lymph nodes. These findings demonstrate a unique R5-tropic SHIV that can be used to study envelope-related issues in vaginal transmission of the most prevalent subtype of HIV-1. We also found that rhesus macaques intravenously inoculated with I x 103 TCID50 of SHIVCHN19P4 became infected and showed CD4+ lymphocytopenia in the gut LPL population. Despite inactivation of the vpu gene in SHIVCHN19P4, the virus appears to target mainly gut-associated lymphoid tissues during the initial stage of infection as has been described for SHIVSF162P, another R5-tropic (subtype B) recombinant virus. Our data indicate that the R5-mediated CD4+ lymphocytopenia in the gut is likely independent of HIV-1 genotypes and of the function of vpu at the acute phase of viral infection.