Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections

Edward J D Greenwood,Vida L Hodara,Leah Clissold,Kirsten Mclay,Bernadette Guerra,Fabian Schmidt,Krishna K Murthy,François Rouet,Robert E Lanford,Henk Niphuis,Jonathan L Heeney,Ivanela Kondova,Sharon Redrobe,Luis D Giavedoni,Guido Silvestri

doi:10.1371/journal.ppat.1005146

Abstract

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in ‘natural host’ species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

Highlights

Over 40 different African primate species are naturally infected with a species-specific simian immunodeficiency virus (SIV) [1]
The HIV-1/AIDS pandemic is the result of cross-species transmission of simian immunodeficiency virus (SIVcpz) from chimpanzees to humans
Many African primates are infected with SIV, but those studied in captivity generally do not develop disease

Summary

Introduction

Over 40 different African primate species are naturally infected with a species-specific simian immunodeficiency virus (SIV) [1]. In a study of wild, Eastern chimpanzees (Pan troglodytes schweinfurthii), in the Gombe National Park, Tanzania, SIVcpz infected animals had a greater risk of mortality, with evidence of CD4+ T cell depletion, indirect evidence of immune activation, and the development of an AIDS like disease in one animal [7] These findings are radically different from the outcome of SIV infection in African green monkeys [8,9] and sooty mangabeys [10], studied in primate research centres, and it has been suggested that the virus-host relationship between SIVcpz and the chimpanzee differs from that found in other species. It has been proposed that this is either due to a more recent acquisition of SIV in chimpanzees, or due to the presence of viral features of SIVcpz, not found in other SIVs (including the presence of the vpu gene and the failure of the SIVcpz nef gene to down-regulate the T-cell receptor [11])

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Results

Discussion

Conclusion