Virus Load and Sequence Variation in Simian Retrovirus Type 2 Infection

Abstract

The natural history of type D simian retrovirus (SRV) infection is poorly characterized in terms of viral load, antibody status, and sequence variation. To investigate this, blood samples were taken from a small cohort of mostly asymptomatic cynomolgus macaques (Macaca fascicularis), naturally infected with SRV type 2 (SRV-2), some of which were followed over an 8-month period with blood taken every 2 months. Provirus and RNA virus loads were obtained, the samples were screened for presence of antibodies to SRV-2 and neutralizing antibody titers to SRV-2 were assayed. env sequences were aligned to determine intra-and intermonkey variation over time. Virus loads varied greatly among cohort individuals but, conversely, remained steady for each macaque over the 8-month period, regardless of their initial levels. No significant sequence variation was found within an individual over time. No clear picture emerged from these results, which indicate that the variables of SRV-2 infection are complex, differ from those for lentivirus infection, and are not distinctly related to disease outcome.The simian retroviruses (SRVs) are type D retroviruses only distantly related to the lentiviruses. They infect various Asian macaque species and can cause a fatal immune deficiency (7,11,12,13,22,30), similar to that induced by simian immunodeficiency virus (SIV) in macaques. Of the five simian retrovirus neutralization serotypes identified (SRV-1 to SRV-5), three (SRV-1 to SRV-3) have been molecularly cloned and genomically sequenced (27,29,34). Disease caused by the more commonly found SRV-2 infection in macaques is characterized by diarrhea, fever, chronic weight loss, anemia, and sometimes retroperitoneal fibromatosis, a tumor of connective tissue origin (21). As in SIV infection, secondary opportunistic infections often develop in diseased monkeys (13,25).Type D retroviruses emerged as serious pathogens associated with immune deficiency between 1983 and 1985 to devastating effect in primate centers across the United States, including those in New England, California, Oregon, and Washington (7,21,30). The prevalence of type D retrovirus infection in these breeding colonies reached epidemic proportions; in the California Primate Center, for example, almost all adult macaques were infected with either SRV-1 or SRV-2 and the mortality rate among juveniles less than 2 years of age approached 50% (17). This was particularly disturbing since these monkeys represented a large proportion of primates used for biomedical research. Thus, considering the severity and frequency of disease caused by SRV-2 infection in macaque breeding populations, it is surprising that so few data exist on the probable correlates of disease, such as proviral copy numbers, RNA plasma levels, and antibody status. These variables are critical in determining the course of other retroviral disease therapy in humans, such as human immunodeficiency virus (HIV)-infected individuals (5, 6, 26). We have therefore hypothesized in this investigation that the course of S...

Evidence of Infection with Simian Type D Retrovirus in Persons Occupationally Exposed to Nonhuman Primates

“…The findings seen in subject 1 are consistent with data obtained from macaques that are naturally infected with SRV (18,20,29). SRV infection in macaques is thought to result in persistent infection, although SRV may become latent in the face of a vigorous immune response (18).…”

“…Spouses of both persons were unavailable for testing to determine whether this SRV seroreactivity is transmissible to humans, and while the absence of disease in both subjects is reassuring, our information is limited by the small sample size, the relatively short length of follow-up, and the absence of clinical observations coincident with infection and seroconversion. However, the anti-SRV neutralizing-antibody titers seen in both seropositive persons may offer them some degree of immunologic protection from viremia and subsequent disease manifestation, as has been recently observed in SRV-2-infected macaques with similar antibody titers and low or undetectable viral loads (29).…”

Persistence and Dissemination of Simian Retrovirus Type 2 DNA in Relation to Viremia, Seroresponse, and Experimental Transmissibility in Macaca fascicularis

“…ELISA data for these three animals indicated that serological responses and viremia are inversely related, as previously noted (15,28). 977G had a minimal antibody response against SRV, whereas 540FC and 963DBDA had strong antibody responses.…”

“…Most importantly for diagnostic purposes, the LTR assay detected all viremic animals. It is interesting that almost half of the viremic animals in the cross-sectional study were env assay negative (env PCR assays designed to detect alternative serogroups, SRV-1 and SRV-3, also failed to amplify any sequence in DNA from one such individual); we propose that minor variation in the SRV env sequence of virus of serogroup 2, as has been reported previously (18,28), could account for this. Viremia and virus replication would be expected to result in the generation of more sequence variants.…”

Morphine Induces Gene Expression of CCR5 in Human CEM x174 Lymphocytes

“…Thus, one yet-to-be-proved mechanism of morphine-mediated up-regulation of CCR5 is through the down-regulation of chemokine synthesis. SRV are endemic in wild macaques of India and Indonesia and in captive macaques important for medical research (33). Five distinct neutralization serotypes (SRV1-SRV5) have been described, of which three have been molecularly cloned (SRV1-SRV3).…”