Multiple human immunodeficiency virus type-1 sequences from the V3 and V4-V5 regions of the envelope gene were analyzed from three mother-infant pairs. The infants' viral sequences were less diverse than those of their mothers. In two pairs, a proviral form infrequently found in the mother predominated in her infant. A conserved N-linked glycosylation site within the V3 region, present in each mother's sequence set, was absent in all of the infants' sequence sets. These findings demonstrate that a minor subset of maternal virus is transmitted to the infant.

Retroviruses may cause diseases in their vertebrate hosts. They are distinguished by their common means of replication involving reverse transcription, a process inhibited by nucleoside reverse transcriptase inhibitors (NRTIs) and other compounds used in antiretroviral chemotherapy. Previous work on NRTIs has been limited to their effect on human immunodeficiency virus (HIV) (for review see Ho & Hitchcock, 1989; Weller, 1999) and little information exists regarding the efficacy and therapeutic potential of these drugs against other retroviruses. We have tested all six NRTIs licensed for HIV treatment [didanosine (ddI), zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), zidovudine (AZT) and abacavir (ABC)] against seven retroviruses representative of the traditional subfamilies: Spumavirinae, Lentivirinae and the Oncovirinae. As expected, each drug showed a range of activities against the panel of retroviruses, some drugs inhibiting other viruses at concentrations well below those required for HIV. Overall, AZT was the most active inhibitor (IC50 range, 0.032–1.0 μM), being most active against the Spuma (foamy) viruses. Abacavir was inhibitory for HIV-1, MN strain (HIV-1 MN), amphotrophic murine leukemia virus (MLV-A) and simian foamy virus type 6 (SFV-6). The least effective inhibitor, 3TC (IC50 range, 0.32–>100 μM), was most potent against simian retrovirus types 1 and 2 (SRV-1, SRV-2) and HIV-1, but did not inhibit foamy viruses and MLV-A. Additionally, there were differences in the concentration of drug required to inhibit closely related viruses. Taken together, these data suggest that NRTIs have a wide spectrum of antiretroviral activity and the activity of compounds, even against closely related retroviruses, cannot be predicted.

Mitochondrial DNA variation was surveyed in nine populations of the pigtail macaque (Macaca nemestrina), covering all three recognized subspecies in Southeast Asia. To do this, a 2,300 base pair fragment spanning the mitochondrial NAD 3 and NAD 4 genes and flanking tRNA subunits leucine and glycine was targeted for amplification and digested with a battery of 16 restriction endonucleases. Out of a total of 107 individuals, 32 unique haplotypes could be distinguished. Parsimony and neighbor-joining analyses grouped the haplotypes into five strongly supported assemblages representing China/Thailand, Malaysia, Sumatra, Borneo, and Siberut. These results indicate that the mainland and island mtDNA haplotypes are strictly and uniquely limited to the geographic ranges of the recognized morphological subspecies. Cladistic and neighbor-joining analyses indicate that inferred phylogenies of mtDNA haplotypes are congruent with subspecies designations. Furthermore, in support of morphological studies, results indicate that the Mentawai macaque is most likely not a distinct species but a subspecies of M. nemestrina.

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...

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