Classic AIDS in a Sooty Mangabey after an 18-Year Natural Infection

Abstract

Prevailing theory holds that simian immunodeficiency virus (SIV) infections are nonpathogenic in their natural simian hosts and that lifelong infections persist without disease. Numerous studies have reported that SIV-infected sooty mangabeys (SMs; Cercocebus atys) remain disease free for up to 24 years despite relatively high levels of viral replication. Here, we report that classic AIDS developed after an 18-year incubation in an SM (E041) with a natural SIVsm infection. Unlike that described in previous reports of SIV-related disease in SMs, the SIVsm infecting E041 was not first passaged through macaques; moreover, SM E041 was simian T-cell leukemia virus antibody negative. SM E041 was euthanized in 2002 after being diagnosed with severe disseminated B-cell lymphoma. The plasma virus load had been approximately the same for 16 years when a 100-fold increase in virus load occurred in years 17 and 18. Additional findings associated with AIDS were CD4 ؉ -cell decline, loss of p27 core antibody, and loss of control of SIVsm replication with disseminated giant cell disease. These findings suggest that the time to development of AIDS exceeds the average lifetime of SMs in the wild and that the principal adaptation of SIV to its natural African hosts does not include complete resistance to disease. Instead, AIDS may develop slowly, even in the presence of high virus loads. However, a long-term relatively high virus load, such as that in SM E041, is consistent with AIDS development in less than 18 years in humans and macaques. Therefore, the results also suggest that SMs have a special mechanism for resisting AIDS development.

Correlates of Preserved CD4+ T Cell Homeostasis during Natural, Nonpathogenic Simian Immunodeficiency Virus Infection of Sooty Mangabeys: Implications for AIDS Pathogenesis

“…SIV-infected SMs typically maintain normal CD4 ϩ T cell counts and do not develop AIDS despite intensive virus replication, with levels of plasma viremia that are as high, or even higher, than those observed in HIV-infected individuals (9 -11). At present, there is only one report of AIDS in a naturally SIV-infected SM (12). In all, these observations are in marked contrast with the known pathogenicity of both the HIV infection of humans and the experimental SIV infection of RMs, where high levels of virus replication are a strong predictor of more rapid disease progression (13)(14)(15)(16).…”

Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

“…However, this CD4 depletion is not associated with major immune activation or viralload increase (26). Immunodeficiency associated with CD4 depletion was reported in only one case (18). Schindler et al discovered that in sooty mangabeys showing a loss of CD4 ϩ T cells, the Nef protein of the infecting SIVsmm was less efficient at TCR downregulation (22), suggesting that the CD4 depletion in sooty mangabeys is linked to the loss of this function, together with a loss of major histocompatibility complex class I downregulation (23).…”

Simian immunodeficiency virus types 1 and 2 (SIV mnd 1 and 2) have different pathogenic potentials in rhesus macaques upon experimental cross-species transmission

“…Unlike pathogenic human immunodeficiency virus (HIV) in humans and SIV in macaques, natural SIV infections generally do not progress to acquired immune deficiency syndrome (AIDS) (Chakrabarti, 2004;Hirsch, 2004;Muller & Barré-Sinoussi, 2003;Norley et al, 1999;Onanga et al, 2002Onanga et al, , 2006Pandrea et al, 2008b;Silvestri, 2005). In fact, only a handful of cases of immunodeficiency have been described to date in African NHP species, all of which have occurred in captive animals (Ling et al, 2004;Pandrea et al, 2001;Traina-Dorge et al, 1992). This lack of SIV-related disease progression in natural NHP hosts does not appear to be due to better infection control, as natural SIV infections are characterized by high levels of virus replication and + T-cell restoration during the chronic infection to near-baseline levels (Kaur et al, 1998;Kornfeld et al, 2005;Pandrea et al, 2005Pandrea et al, , 2006Silvestri et al, 2005).…”