Simian Immunodeficiency Virus (SIV) is a primate virus belonging to the genus Lentivirus, a subgroup of the Retroviridae family, characterized by causing slowly progressing, persistent infections. SIV naturally infects a wide variety of non-human primates (NHPs) across Africa, establishing a chronic presence. Studying SIV is integral to understanding lentiviral infections.
Defining SIV and Its Natural Hosts
SIV is not a single pathogen but a collection of distinct viruses, each specifically adapted to infect different species of African monkeys and apes. Scientists have identified SIV strains in over 40 species of African non-human primates, including African green monkeys, sooty mangabeys, and chimpanzees. The classification of SIV as a lentivirus places it in the same genus as the Human Immunodeficiency Virus (HIV).
These African primates are considered the “natural hosts” because the virus has co-evolved with them. In these natural hosts, the SIV infection is typically non-pathogenic. Despite maintaining high viral levels, these animals generally do not develop the progressive immune system failure seen in untreated HIV infection.
Disease Progression in Primates
The outcome of SIV infection depends fundamentally on the host species, leading to two distinct patterns of disease progression. Natural hosts like the sooty mangabey exhibit a non-pathogenic infection, where the immune system successfully manages the viral presence without collapsing. The defining feature of this non-pathogenic state is the host’s ability to limit chronic immune activation and inflammation, even with high viral replication rates.
In these species, there is preservation of CD4+ T-cells, the immune cells targeted by the virus, and a lack of the generalized immune activation that drives disease progression. The low expression of the CCR5 co-receptor on CD4+ T-cells in natural hosts is one mechanism that helps preserve the immune integrity. In sharp contrast, a pathogenic infection, or Simian AIDS, occurs when SIV infects a non-natural host, such as the rhesus macaque in a laboratory setting.
The progression of Simian AIDS in non-natural hosts closely mirrors the disease in humans with untreated HIV, characterized by chronic, generalized immune activation. This sustained inflammation leads to a relentless depletion of CD4+ T-cells, which compromises the immune system’s function. The loss of these T-cells and the subsequent immune failure result in opportunistic infections and cancers, which define the final stages of the disease.
SIV as the Origin of HIV
SIV is widely studied due to its direct evolutionary relationship with HIV, the virus that causes AIDS in humans. HIV is the result of multiple zoonotic transfer events, where SIV crossed the species barrier from non-human primates to humans. Specifically, the most common form, HIV-1, originated from the SIV strain found in chimpanzees, known as SIVcpz.
Evidence suggests that the transfer of SIVcpz to humans occurred on multiple, independent occasions, resulting in the different genetic groups of HIV-1. The globally dominant HIV-1 Group M, which is responsible for the vast majority of the human pandemic, arose from one of these separate cross-species transmissions. The most likely route of transmission was through contact with infected blood during the hunting and butchering of primates for bushmeat.
The second type, HIV-2, has a separate origin, stemming from SIV found in sooty mangabeys, referred to as SIVsmm. Like HIV-1, HIV-2 also resulted from multiple cross-species jumps from mangabeys to humans in West Africa. These independent events highlight the ability of lentiviruses to adapt to new hosts, giving rise to the two distinct human viruses.
How SIV is Studied
SIV provides an invaluable animal model for studying HIV/AIDS because the pathogenic infection in non-natural hosts like rhesus macaques closely mimics the human disease. The Simian Acquired Immunodeficiency Syndrome (SAIDS) model allows researchers to observe the entire disease process, from initial infection to advanced immunodeficiency, in a controlled setting. This model is essential for testing the effectiveness and safety of potential treatments before human trials can begin.
Scientists use SIV-infected macaques to evaluate new antiretroviral drugs, which are the cornerstone of HIV treatment. The model also serves as the primary platform for testing candidate HIV vaccines, an area of research that has proven challenging. Furthermore, a chimeric virus called Simian-Human Immunodeficiency Virus (SHIV), which combines parts of the SIV and HIV genomes, is often used to better simulate aspects of the human virus in the macaque model.