Influence of Naturally Occurring Simian Foamy Viruses (SFVs) on SIV Disease Progression in the Rhesus Macaque (Macaca mulatta) Model

Abstract

We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIVmac239 virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV−/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6–28 weeks, particularly after reaching plateau at 20–28 weeks, in the CD4+ and CD8+ T-cell numbers over the entire study period (2–43 weeks), and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4+ T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans.

In Vivo Cellular Tropism of Gorilla Simian Foamy Virus in Blood of Infected Humans

“…Cases of HIV-1/SFV (17) or HTLV-1/SFV (unpublished data) coinfections have been found in humans. In macaques, experimental SIV infection in either non-SFV-infected or naturally SFV-infected animals revealed that SFV infection increases the pathology of SIV infection (18). Given the ongoing risk of exposure to these three primate retroviruses, especially in Central Africa, microbiological surveillance is required to better evaluate the potential clinical and physiopathological impact of such retroviral interactions.…”

A new sensitive indicator cell line reveals cross-transactivation of the viral LTR by gorilla and chimpanzee simian foamy viruses

“…Our results underline the importance of extending current knowledge beyond the most studied prototype strain. Indeed, Tas interacts with promoters from host genes (Colas et al, 1995;Kido et al, 2002;Wagner et al, 2000;Wang et al, 2010), may be involved in clinically relevant interactions with lentiviruses (Choudhary et al, 2013), and is a potential (but still controversial) target of the immune system (Meiering and Linial, 2003;Regad et al, 2001).…”

“…SFVs also merit study for their own potential impact on human health, as vectors for gene therapy and vaccination (Olszko and Trobridge, 2013), and because co-infection with other retroviruses has been reported in humans (Filippone et al, 2015;Switzer et al, 2008). Such a coinfection with SFV has deleterious consequences in macaques experimentally infected with SIV (Choudhary et al, 2013).…”

Eleventh International Foamy Virus Conference—Meeting Report

“…A single study reported histopathological findings in the kidney of FV-inoculated domestic cats indicative of syncytia formation [8]. In a more recent study conducted with simian immunodeficiency virus (SIV)-infected rhesus macaques, Choudhary and colleagues have shown that those coinfected with the simian FV (SFV) progressed faster to the acquired immune deficiency syndrome (AIDS), had higher SIV viral loads and accelerated CD4 + T-cell depletion when compared to animals singly infected with SIV [9]. This raises the possibility that FV can act as an opportunistic pathogen, modulating the pathogenic impact of other infections.…”