Abstract
African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIVagmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.
Highlights
It is not known when simian immunodeficiency virus (SIV) was first introduced into African nonhuman primates, it is widely believed that African monkey and ape species coevolved with SIV infection probably for tens of thousands of years [1,2]
We made a direct comparison of the role of SIV-specific adaptive immune responses in a nonnatural host and natural host of SIV infection, pigtailed macaques (PTM) and vervet African green monkeys (AGM), respectively
We evaluated the effect of antibody-mediated temporal inhibition of cellular and humoral immune responses during primary infection with the uncloned SIV virus, SIVagmVer90, in PTM and AGM
Summary
It is not known when SIV was first introduced into African nonhuman primates, it is widely believed that African monkey and ape species coevolved with SIV infection probably for tens of thousands of years [1,2]. Asian nonhuman primates and humans encountered the virus much more recently [2,3] Despite these differences, SIV infections in nonhuman primates and HIV in humans follow a similar pattern of viremia: an initial burst of viremia during primary infection followed by a partial containment and establishment of a plateau or set point viremia [4,5,6]. Given the similarities in viral load, the course of infection and its consequences differ between natural and nonnatural hosts [11,12,13]. Most natural hosts such as AGM appear to peacefully coexist with the SIV infection while macaques generally develop overt signs of illness, immune failure and AIDS [14]. Recent findings indicate that some natural hosts like chimpanzees may develop an AIDS-like disease when infected with SIV [15]
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