Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1

Abstract

Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4+ T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

The well-tempered SIV infection: Pathogenesis of SIV infection in natural hosts in the wild, with emphasis on virus transmission and early events post-infection that may contribute to protection from disease progression

“…These results are in agreement with studies of experimentally infected AGMs, where sCD14 levels remained stable following infection (Pandrea et al, 2006b, 2012a, 2012a, 2007b). A separate study of semi-wild mandrills in Gabon confirmed these results by showing that plasma levels of sCD14 remained unchanged following SIVmnd1-infection (Greenwood et al, 2014). …”

“…Also, SM CD4 + T CM proliferation levels are lower than in RMs and the RM T CM proliferation correlates with viral replication (McGary et al, 2014). Yet, a recent study of mandrills in Gabon found a significant decrease in memory T-cells populations that was correlated with the duration of infection (Greenwood et al, 2014). However, other studies of the same mandrill cohort did not find similar features (Apetrei et al, 2011).…”

Genome-wide patterns of gene expression in a wild primate indicate species-specific mechanisms associated with tolerance to natural simian immunodeficiency virus infection

“…During this period, one of the hallmark features of nonpathogenic SIV infection is the rapid attenuation of ISG expression to baseline levels in the chronic phase (Bosinger et al 2009;Jacquelin et al 2009;Lederer et al, 2009). Additionally, natural hosts maintain high viral loads, but recover CD4+ T cell homeostasis, though variation in the effects of SIV infection on CD4+ T cell homeostasis have been observed in natural hosts (Keele et al 2009;Greenwood et al, 2014). While the upregulation of ISGs persists in pathogenic SIV/HIV infection in macaques and humans (Paiardini & Müller-Trutwin, 2013), rapid control of ISG expression occurs in natural hosts (AGMs and SMs) within 4-8 weeks post-infection (Bosinger et al 2009;Jacquelin et al 2009).…”

“…Over 40 species of nonhuman primates are naturally infected with endemic strains of SIV, including African apes and African members of the Old World monkey subfamilies Cercopithecinae and Colobinae (VandeWoude & Apetrei, 2006;Worobey et al, 2010). However, studies on the pathogenicity of SIV infection in natural hosts have been limited to chimpanzees and three species within the Cercopithecinae (African green monkey (AGM), sooty mangabey (SM), and mandrill (MND; Apetrei et al, 2011;Bosinger et al, 2009;Greenwood et al, 2014;Jacquelin et al, 2009;Keele et al, 2009;Ma et al, 2013). Recently, studies in SIVcpz-infected chimpanzees (Keele et al, 2009) and SIVmnd-1-infected MNDs (Greenwood et al, 2014) have demonstrated variation in the pathogenic effects of SIV infection in natural hosts, but to our knowledge no study has assessed the relationship between SIV infection and host gene expression patterns in a wild population of natural SIV hosts.…”

“…However, studies on the pathogenicity of SIV infection in natural hosts have been limited to chimpanzees and three species within the Cercopithecinae (African green monkey (AGM), sooty mangabey (SM), and mandrill (MND; Apetrei et al, 2011;Bosinger et al, 2009;Greenwood et al, 2014;Jacquelin et al, 2009;Keele et al, 2009;Ma et al, 2013). Recently, studies in SIVcpz-infected chimpanzees (Keele et al, 2009) and SIVmnd-1-infected MNDs (Greenwood et al, 2014) have demonstrated variation in the pathogenic effects of SIV infection in natural hosts, but to our knowledge no study has assessed the relationship between SIV infection and host gene expression patterns in a wild population of natural SIV hosts. It has become increasingly clear that the effects of SIV infection vary across natural hosts, and the assumption of nonpathogenic SIV infection in natural hosts warrants further testing in a wider breadth of taxa, particularly in understudied groups such as the Colobinae (Bosinger et al, 2013;Palesh et al, 2018).…”