Human Immunodeficiency Virus (HIV) is a retrovirus that primarily infects humans. It targets and destroys CD4-positive T-cells, crucial for fighting infections. Untreated, HIV can lead to acquired immunodeficiency syndrome (AIDS), severely weakening the immune system and making the body vulnerable to opportunistic infections and cancers. While HIV is specific to humans, its origins trace back to viruses in certain animal species.
Simian Immunodeficiency Virus (SIV) and its Natural Hosts
Simian Immunodeficiency Virus (SIV), the evolutionary precursor to HIV, naturally infects numerous non-human primate species in Africa. Over 40 distinct SIV strains circulate in wild African primates, including sooty mangabeys, chimpanzees, and African green monkeys. These SIVs have coexisted with their natural hosts for millennia, typically causing little to no disease, unlike the severe illness seen in humans.
This long co-evolution has allowed primates to adapt mechanisms preventing widespread immune system damage. Zoonotic transmission explains how SIVs jumped from non-human primates to humans on multiple occasions, leading to HIV’s emergence. HIV-1, the globally prevalent strain, originated from SIVs in chimpanzees and gorillas, while HIV-2 is linked to SIVs from sooty mangabeys.
HIV Susceptibility in Non-Human Primates
While SIVs are endemic in African primates, human HIV infection in non-human primates, particularly in experimental settings, is distinct. Chimpanzees can be infected with HIV-1, but they typically do not develop AIDS or severe immune decline. The virus replicates, but infection usually remains asymptomatic, and viral loads often decrease over time.
Macaques, especially pigtailed macaques, have been experimentally infected with HIV-1. However, efficient HIV-1 replication and disease progression in macaques often require viral modifications, such as creating simian-human immunodeficiency viruses (SHIVs) that contain genetic elements from both SIV and HIV. These adapted viruses can cause an AIDS-like disease in macaques, making them important models for studying HIV pathogenesis and testing potential treatments and vaccines. Sooty mangabeys, the natural hosts for SIVs that led to HIV-2, can also be infected with HIV-2.
Susceptibility in Other Animal Species
Beyond primates, the susceptibility of other animal species to human HIV is a common concern. Domestic animals like dogs and cats cannot contract human HIV, as the virus is highly species-specific.
Cats have their own retrovirus, Feline Immunodeficiency Virus (FIV), which affects their immune system similarly to HIV. FIV is distinct from human HIV and is not transmissible to humans.
In research, specialized “humanized mice” are used to study HIV infection. These mice are engineered with human immune cells and tissues, allowing them to be infected with human HIV and mimic aspects of human infection and disease progression. This experimental model provides a valuable tool for HIV research but does not represent natural susceptibility in mice.
Factors Influencing Susceptibility
The ability of HIV or SIV to infect a cell and replicate depends on specific biological factors present in the host. A primary factor is the presence and compatibility of cell surface receptors that the virus uses to enter cells. HIV requires the CD4 receptor on immune cells, along with co-receptors like CCR5 or CXCR4.
The viral envelope protein binds to CD4, triggering a conformational change allowing it to bind a co-receptor, facilitating viral entry. Genetic variations in these receptors can influence susceptibility or resistance. For example, some individuals with a specific genetic mutation in the CCR5 gene are naturally resistant to HIV infection because the virus cannot effectively enter their cells.
Beyond receptors, host restriction factors also play a role in determining viral susceptibility. Proteins like TRIM5α, part of the innate immune system, can recognize and block retroviral replication in a species-specific manner. The variations in these factors across different animal species contribute to why some are susceptible to HIV/SIV while others are not, by blocking the virus at various stages of its life cycle.