Pathogenesis of experimental rhesus cytomegalovirus infection

Human cytomegalovirus (HCMV) establishes and maintains a lifelong persisten ce following infection in an immunocompetent host. The determinants of a st able virus-host relationship are poorly defined, A nonhuman primate model f or HCMV was used to investigate virological and host parameters of infectio n in a healthy host. Juvenile rhesus macaques (Macaca mulatta) mere inocula ted with rhesus cytomegalovirus (RhCMV), either orally or intravenously (i. v.), and longitudinally necropsied. None of the animals displayed clinical signs of disease, although hematologic abnormalities were observed intermit tently in i.v. inoculated animals. RhCMV DNA was detected transiently in th e plasma of all animals at 1 to 2 weeks postinfection (wpi) and in multiple tissues beginning at 2 to 4 wpi. Splenic tissue was the only organ positiv e for RhCMV DNA in all animals. The location of splenic cells expressing Rh CMV immediate-early protein 1 (IE1) in i.v. inoculated animals changed foll owing inoculation. At 4 to 5 wpi, most IE1-positive cells were perifollicul ar, and at 25 wpi, the majority were located within the red pulp. All anima ls developed anti-RhCMV immunoglobulin M (IgM) antibodies within I to 2 wpi and IgG antibodies within 2 to 4 wpi against a limited number of viral pro teins. Host reactivity to RhCMV proteins increased in titer (total and neut ralizing) and avidity with time, These results demonstrate that while antiv iral immune responses were able to protect from disease, they were insuffic ient to eliminate reservoirs of persistent viral gene expression.