Case-Control Study of the Immune Status of Humans Infected With Zoonotic Gorilla Simian Foamy Viruses

Abstract

Background Zoonotic simian foamy viruses (SFVs) establish persistent infections in humans, for whom the long-term consequences for health are poorly described. In this study, we aimed to characterize blood-cell phenotypes and plasma biomarkers associated with gorilla SFV infection in humans. Methods We used a case-control design to compare 15 Cameroonian hunters infected with gorilla SFV (cases) to 15 controls matched for age and ethnicity. A flow cytometry-based phenotypic study and quantification of plasma immune biomarkers were carried out on blood samples from all participants. Wilcoxon signed-rank tests were used to compare cases and controls. Results Cases had a significantly higher percentage of CD8 T lymphocytes than controls (median, 17.6% vs 13.7%; P = .03) but similar levels of B, natural killer, and CD4 T lymphocytes. Cases also had a lower proportion of recent CD4 thymic emigrants (10.9% vs 18.6%, P = .05), a higher proportion of programmed death receptor 1 (PD-1) expressing memory CD4 T lymphocytes (31.7% vs 24.7%, P = .01), and higher plasma levels of the soluble CD163 scavenger receptor (0.84 vs .59 µg/mL, P = .003) than controls. Conclusions We show, for the first time, that chronic infection with SFV is associated with T lymphocyte differentiation and monocyte activation.

Comparison of a Genotype 1 and a Genotype 2 Macaque Foamy Virus env Gene Indicates Distinct Infectivity and Cell-Cell Fusion but Similar Tropism and Restriction of Cell Entry by Interferon-Induced Transmembrane Proteins

“…Nevertheless, our results suggest that foamy viruses may be able to quickly acquire enhanced fitness through acquisition of a different env gene through recombination, which would, in the case studied here, result in increased cell-cell fusion and at the same time release of higher absolute infectivity and higher per-particle infectivity. Given the known very high propensity to template switching of foamy viruses [ 54 ], the possibility of such recombination events should be kept in mind in light of the well-known zoonotic potential [ 9 , 10 , 11 , 12 , 13 , 52 ]. Frequent exchange of the variant parts of env has been proposed as one possible explanation for the high evolutionary stability of the foamy virus genome and its diversity in the env gene [ 22 ].…”

“…Endogenous foamy viruses are present in coelacanth [ 5 ], amphibia [ 6 ], fish [ 7 ], birds and serpentines [ 8 ]. SFVs have demonstrated a potential for zoonotic infection in Africa [ 9 , 10 , 11 ] and also in Asia [ 12 , 13 ]. Recently, zoonotic infections with gorilla SFV were found to be associated with hematological abnormalities and altered biochemical markers [ 9 ].…”

Foamy Viruses, Bet, and APOBEC3 Restriction

“…This area of research is particularly interesting because FV infections are apparently apathogenic in the hosts, but in vitro, FV infection triggers cytopathic effects and ultimately leads to cell death [22]. However, recent case-control studies among Cameroonian hunters infected with gorilla SFV identified an association of T-cell differentiation, monocyte activation, and hematological abnormalities with SFV infection [112,113]. These and a similar study that characterized an association of FFV with chronic kidney disease in cats [114] suggest that more research is needed to explore in vivo pathological changes by FVs.…”

Epidemiological Survey and Risk Factor Analysis of 14 Potential Pathogens in Golden Snub-Nosed Monkeys at Shennongjia National Nature Reserve, China

“…Humans can be infected by monkey bites and scratches and develop fetal encephalitis with a mortality exceeding 70% in the absence of treatment and 20% even with adequate treatment [ 13 ]. SFV is ubiquitous in several primate species and usually causes persistent infection [ 14 , 15 ], whereas SFV infections in humans are well documented to cause subclinical hematologic changes [ 16 , 17 , 18 ]. In addition, Adenovirus and Rotavirus are important zoonotic pathogens that might lead to high rates of mortality in humans and animals [ 19 , 20 , 21 ].…”