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Foamy viruses are complex retroviruses that have been shown to be transmitted from nonhuman primates to humans. In Bangladesh, infection with simian foamy virus (SFV) is ubiquitous among rhesus macaques, which come into contact with humans in diverse locations and contexts throughout the country. We analyzed microsatellite DNA from 126 macaques at six sites in Bangladesh in order to characterize geographic patterns of macaque population structure. We also included in this study 38 macaques owned by nomadic people who train them to perform for audiences. PCR was used to analyze a portion of the proviral gag gene from all SFV-positive macaques, and multiple clones were sequenced. Phylogenetic analysis was used to infer long-term patterns of viral transmission. Analyses of SFV gag gene sequences indicated that macaque populations from different areas harbor genetically distinct strains of SFV, suggesting that geographic features such as forest cover play a role in determining the dispersal of macaques and SFV. We also found evidence suggesting that humans traveling the region with performing macaques likely play a role in the translocation of macaques and SFV. Our studies found that individual animals can harbor more than one strain of SFV and that presence of more than one SFV strain is more common among older animals. Some macaques are infected with SFV that appears to be recombinant. These findings paint a more detailed picture of how geographic and sociocultural factors influence the spectrum of simian-borne retroviruses.

The E2 ubiquitin conjugation enzyme Cdc34 acts in conjunction with an E3 ubiquitin ligase complex composed of Skp1, Cdc53 and F-box protein, Cdc4 (the SCF super Cdc4 complex) to catalyze ubiquitination of the cyclin-dependent kinase (Cdk) inhibitor Sic1 in budding yeast. Cdc53 is a scaffold protein for various Cdc34/Skp1/F-box protein complexes that control yeast cell division and methionine biosynthesis. F-box proteins have great functional specificity in vivo.

Experiment was conducted to explore the role of Skp1 and F-box proteins in ubiquitination through in vitro reconstruction of the Sic1 ubiquitination pathway. Skp1 functions to recruit Cdc-4 into a Cdc53/Cdc-34 complex and enhances recognition of Sic1 by Cdc4, the latter interaction requiring Sic1 phosphorylation. In comparison, Grr1 does not interact with Sic1 but recruits phosphorylated Cln1 and Cln2 into Skp1/Cdc53 complexes. Results suggest that F-box proteins function as receptors that recruit substrates into a Skp1/Cdc53/Cdc34 complex for ubiquitination.

Proteins that interact with the G1 cyclin Cln2 that helps activate cell division in budding yeast are studied. Immunoaffinity column chromatography is used to identify the proteins, with a CLN2 allele being tagged with a triple hemagluttinin epitope to allow specific detection of Cln2-associated proteins. Cdc53 is isolated as a Cln2-associated protein and shown to be required for Cln2 instability and ubiquitination in vivo.

Foamy viruses (FV) are complex retroviruses that naturally infect all nonhuman primates (NHP) studied to date. Zoonotic transmission of Old World NHP simian foamy viruses (SFV) has been documented, leading to nonpathogenic persistent infections. To date, there have been no reports concerning zoonotic transmission of New World monkey (NWM) SFV to humans and resulting infection. In this study, we developed a Western blot assay to detect antibodies to NWM SFV, a nested PCR assay to detect NWM SFV DNA, and a galactosidase-containing indicator cell line to assay replication of NWM SFV. Using these tools, we analyzed the plasma and blood of 116 primatologists, of whom 69 had reported exposures to NWM. While 8 of the primatologists tested were seropositive for SFV from a NWM, the spider monkey, none had detectable levels of viral DNA in their blood. We found that SFV isolated from three different species of NWM replicated in some, but not all, human cell lines. From our data, we conclude that while humans exposed to NWM SFV produce antibodies, there is no evidence for long-term viral persistence. [ABSTRACT FROM AUTHOR]