Experimental infection of rhesus and pig-tailed macaques with macaque rhadinoviruses

The recognition of naturally occurring rhadinoviruses in macaque monkeys ha s spurred interest in their use as models for human infection with Kaposi s arcoma-associated herpesvirus (human herpesvirus 8). Rhesus macaques (Macac a mulatta) and pig-tailed macaques (Macaca nemestrina) were inoculated intr avenously with rhadinovirus isolates derived from these species (rhesus rha dinovirus [RRV] and pig-tailed rhadinovirus [PRV]), Nine rhadinovirus antib ody-negative and two rhadinovirus antibody-positive monkeys were used for t hese experimental inoculations. Antibody-negative animals clearly became in fected following virus inoculation since they developed persisting antibody responses to virus and virus was isolated from peripheral blood on repeate d occasions following inoculation. Viral sequences were also detected by PC R in lymph node, oral mucosa, skin, and peripheral blood mononuclear cells following inoculation. Experimentally infected animals developed peripheral lymphadenopathy which resolved by 12 weeks following inoculation, and thes e animals have subsequently remained free of disease. No increased pathogen icity was apparent from cross-species infection, i.e., inoculation of rhesu s macaques with PRV or of pig-tailed macaques with RRV, whether the animals were antibody positive or negative at the time of virus inoculation. Coino culation of additional rhesus monkeys with simian immunodeficiency virus (S IV) isolate SIVmac251 and macaque-derived rhadinovirus resulted in an atten uated antibody response to both agents and shorter mean survival compared t o SIVmac251-inoculated controls (155.5 days versus 560.1 days; P < 0.019). Coinfected and immunodeficient macaques died of a variety of opportunistic infections characteristic of simian AIDS. PCR analysis of sorted peripheral blood mononuclear cells indicated a preferential tropism of RRV for CD20() B lymphocytes. Our results demonstrate persistent infection of macaque mo nkeys with RRV and PRV following experimental inoculation, but no specific disease was readily apparent from these infections even in the context of c oncurrent SIV infection.