| |
HIV Can Kill Chimps; Infectious diseases: An ill wind for wild chimps?
|
| |
| |
Robin A. Weiss1 & Jonathan L. Heeney2
Nature 460, 470-471 (23 July 2009)
Abstract
Simian immunodeficiency virus is associated with increased mortality in a subspecies of chimpanzee living under natural conditions in East Africa. This is worrying news for the chimpanzee populations involved.
Today's pandemic strain of HIV-1 crossed the species barrier from chimpanzees (Pan troglodytes) to humans less than 100 years ago. Until now, it has been widely assumed that the precursor of HIV-1, chimpanzee simian immunodeficiency virus (SIVcpz), causes little, if any, illness in its animal host. On page 515 of this issue, however, Keele and colleagues1 show that small groups of wild chimpanzees naturally infected with SIVcpz do develop hallmarks of AIDS. Careful monitoring for almost a decade has revealed that SIV-infected animals of the eastern subspecies of chimpanzee (Pan troglodytes schweinfurthii) in the Gombe National Park in Tanzania have a markedly higher death rate than non-infected animals.
Chimpanzees - humans' closest living relative - are not only genetically similar to humans but also share susceptibility to some infectious diseases. For instance, outbreaks of haemorrhagic fever caused by relatives of Ebola virus in chimpanzees and gorillas have resulted in marked mortality in wild populations2. However, subtle chronic diseases like those caused by lentiviruses such as SIV/HIV are more difficult to document in wild non-human primates than are acute diseases with high mortality rates.
More than 40 strains of SIV are known to cause natural infection in African non-human primates3, but few cases of AIDS have been recorded, and progression to illness after viral infection is thought to be rare. This lack of disease has been well documented in African green monkeys and sooty mangabeys4. In addition, a captive P. t. schweinfurthii is in good health almost 20 years after being identified as having naturally acquired SIVcpz infection (Fig. 1). However, exceptions have been noted in primates in captivity. For example, a captive sooty mangabey developed classic symptoms of AIDS 18 years after natural infection with SIV5. This long incubation period exceeded the average lifespan of sooty mangabeys in the wild and, because the adaptation of SIV to its natural simian hosts would not necessarily include complete avirulence, it is difficult to draw conclusions from this isolated example. AIDS has also been documented in black mangabeys in captivity following transmission of SIVsm from sooty mangabeys, their naturally infected cousins4.
Noah, the first Pan troglodytes schweinfurthii to be identified with naturally acquired SIVcpz infection, is alive and well almost 20 years later. By contrast, a number of SIVcpz-infected chimpanzees in the wild seem to develop an AIDS-like illness.
The outcome of infection with HIV or SIV is determined both by variants of the viral population and by individual host differences. In studies conducted largely in the 1980s, chimpanzees (mostly of the subspecies Pan troglodytes verus) that were infected with a particular laboratory strain of HIV-1 controlled the amount of virus in the blood, and remained healthy, although a human accidentally exposed to the same strain of HIV-1 developed AIDS6. A report of one case indicated that certain variants of HIV-1 can cause disease in chimpanzees7. However, such experiments are no longer permitted owing to the endangered status of chimpanzees.
Keele et al.1 are the first to examine the long-term effects of naturally transmitted SIVcpz in wild chimpanzee populations in their natural habitat. The research was made possible because the Gombe chimpanzees have been studied in their natural setting for many decades by Jane Goodall and colleagues, and these animals are accustomed to the presence of humans. Samples of faeces collected from the forest floor can be used to detect SIVcpz DNA and the infected individual can be identified by performing genetic fingerprinting on the same sample. In addition, antibodies directed against SIVcpz can be detected in urine. Using such techniques, 94 members of social groups of chimpanzees in Gombe were meticulously followed over a 9-year period without the need to capture them or take blood samples to determine rates of SIVcpz infection and its effects. Overall, 17 (18%) apes were infected with SIVcpz. Several infected animals that died were autopsied, revealing pathology compatible with human AIDS. The SIV-infected apes had a 10- to 16-fold higher mortality rate than did non-infected apes, and a smaller proportion of infected females gave birth to offspring, none of which survived for more than one year.
SIVcpz in chimpanzees is apparently less virulent than HIV-1 is in humans. Why? One hypothesis8 is that SIVcpz and its chimpanzee host have co-evolved over millions of years. But SIVcpz may in fact be a relatively recent introduction into chimpanzees - it seems to be a recombinant virus with genome components from SIVs of other monkeys, such as red-capped mangabeys and guenons9. A recent report10 estimates that the time of the most recent common ancestor of the SIVcpz strains of all chimpanzee subspecies is 1492, although this calculation is likely to be hotly debated. Alternative explanations for differences in virulence between HIV-1 and SIVcpz could be the immune status or evolved immune genetics of the affected populations, including differences among species in host factors that restrict certain types of viral infection9.
The Gombe chimpanzees belong to the eastern subspecies P. t. schweinfurthii. The western subspecies Pan troglodytes troglodytes, which harbours the SIVcpz variants that have given rise to HIV-1, has not yet been identified with AIDS-like illness (Fig. 2). Could the increased virulence of SIVcpz in P. t. schweinfurthii be due to a recent cross-subspecies transmission of SIVcpz from P. t. troglodytes to an immunologically naive P. t. schweinfurthiipopulation? It is notable that SIVcpz of the P. t. troglodytes subspecies has transmitted to humans on at least three occasions, whereas SIVcpz cross-infection to humans from P. t. schweinfurthii has not been documented.
There are four extant subspecies of common chimpanzee: Pan troglodytes verus, Pan troglodytes vellerosus, Pan troglodytes troglodytes and Pan troglodytes schweinfurthii. The distribution of the pygmy chimpanzee, or bonobo, Pan paniscus, is also shown. Only the subspecies P. t. troglodytes and P. t. schweinfurthii are known to harbour SIVcpz. Gombe National Park in Tanzania (the site of Keele and colleagues' study1) is at the most eastern border of P. t. schweinfurthii territory. The precursor of SIVcpz is believed to be a genetic recombinant of lentiviruses found in two species of monkey, red-capped mangabeys (Cercocebus torquatus) and guenons (genus Cercopithecus) in west-central Africa. The west-central subspecies P. t. troglodytes, which harbours the SIVcpz variants that gave rise to HIV-1 of humans and SIVgor of gorillas, may have spread eastward to P. t. schweinfurthii causing disease.
In view of Keele and colleagues' results1, why was the progression of SIV infection to AIDS-like illness not more apparent in chimpanzees in captivity? Much of the pathology of AIDS is linked to a general hyperactivation of the immune system that occurs before CD4 T-cell depletion, which is characteristic of AIDS11. Certainly the parasitic, bacterial and viral burden inP. t. schweinfurthii chimpanzees in their natural habitat might provide the activating environment to trigger progression to AIDS in a relatively immunologically naive subspecies. General theories of the evolution of virulence, and of the relationship between virulence and pathogen dispersal12, can help in elucidating why certain infections cause disease whereas others don't - the abrupt changes in virulence on cross-host infection are ripe for modelling, taking into account the burgeoning knowledge of host genetic variation. Primate lentiviruses would be a promising starting point for this exercise.
The study by Keele et al.1 shows the benefit of multidisciplinary research, in which primatologists, pathologists, geneticists and molecular virologists joined forces. Their work indicates that SIVcpz causes AIDS-like disease in a subspecies of chimpanzee that is already endangered in the wild. In addition to the threat of AIDS and Ebola, the great apes may also be at risk of acquiring other infections that affect humans from their increasingly close contact with our species. Relatively minor human infections could prove to be serious pathogens in chimpanzees. We are not alone.
References
1. Keele, B. F. et al. Nature 460, 515-519 (2009).
2. Bermejo, M. et al. Science 314, 1564 (2006).
3. Aghokeng, A. F. et al. Infect. Genet. Evol.doi:10.1016/j.meegid.2009.04.014 (2009).
4. Pandrea, I., Silvestri, G. & Apetrei, C. Curr. HIV Res. 7, 57-72 (2009).
5. Ling, B. et al. J. Virol. 78, 8902-8908 (2004).
6. Beaumont, T. et al. J. Virol. 75, 2246-2252 (2001).
7. Novembre, F. J. et al. J. Virol. 71, 4086-4091 (1997).
8. de Groot, N. G. et al. Proc. Natl Acad. Sci. USA 99, 11748-11753 (2002).
9. Heeney, J. L., Dalgleish, A. G. & Weiss, R. A. Science 313, 462-466 (2006).
10. Wertheim, J. O. & Worobey, M. PLoS Comput. Biol. 5, e1000377 (2009).
11. Gougeon, M. L. et al. J. Immunol. 158, 2964-2976 (1997).
12. Wild, G., Gardner, A. & West, S. A. Nature 459, 983-986 (2009).
1. Robin A. Weiss is in the Division of Infection and Immunity, University College London, London W1T 4JF, UK.
Email: r.weiss@ucl.ac.uk
2. Jonathan L. Heeney is in the Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
Email:jlh66@cam.ac.uk
|
|
| |
| |
|
|
|
