Primate lentiviruses

Primate lentiviruses, which include Simian Immunodeficiency Viruses (SIV) and Human Immunodeficiency Viruses (HIV-1 and HIV-2), are responsible for chronic immunodeficiency diseases in primates, including humans, and are closely related in structure and function.

The pandemic HIV-1 M group is thought to have originated via zoonotic transfer from chimpanzees (left).
HIV-1 infects human T-lymphocytes (middle) causing chronic, persistent infections.
The development of combination antiretroviral therapy (right) has provided options for treatment of HIV infection. However, no practical cure exists and constant surveillance of antiretroviral drug resistance is required to preserve the effectiveness of current regimens, especially in resource-limited regions.

Transmission:

• Primate lentiviruses are primarily blood-borne and transmitted through:
  • Sexual contact (most common mode in humans).
  • Mother-to-child transmission (vertical transmission), which can occur during childbirth or through breastfeeding.
  • Blood-to-blood contact through contaminated needles, blood transfusions, or open wounds.
• SIV in non-human primates is often transmitted through biting, grooming, and in some species, through sexual transmission.

Pathogenesis:

• Primate lentiviruses infect CD4+ T-cells, macrophages, and dendritic cells, progressively destroying the immune system over time.
• The viral infection leads to a gradual decline in the immune system, eventually causing Acquired Immunodeficiency Syndrome (AIDS) in humans or simian AIDS in primates.
• SIV infection in its natural primate hosts (e.g., sooty mangabeys and African green monkeys) often remains non-pathogenic, as these species have co-evolved with the virus and typically do not develop AIDS.

Clinical Signs:

HIV-1 and HIV-2 in Humans:

1. Acute HIV infection (primary stage):

   • Occurs 2-4 weeks after exposure.
   • Symptoms resemble flu or mononucleosis, including fever, rash, swollen lymph nodes, and sore throat.
   • High levels of virus are present in the blood during this phase.

2. Chronic HIV infection (clinical latency):

   • Can last for years, with few or no symptoms.
   • The virus continues to replicate at low levels, progressively weakening the immune system.

3. AIDS:

   • The immune system is severely compromised, leading to opportunistic infections (e.g., tuberculosis, pneumonia, fungal infections), cancers (e.g., Kaposi's sarcoma), and wasting syndrome.
   • CD4+ T-cell counts fall below 200 cells/µL (normal is 500-1,500 cells/µL).

SIV in Non-Human Primates:

1. Pathogenic SIV infection (in primates like rhesus macaques):

   • Symptoms mimic those seen in AIDS, including chronic diarrhea, weight loss, opportunistic infections, and eventual death.

2. Non-pathogenic SIV infection (in natural hosts like sooty mangabeys):

   • Infected animals often remain asymptomatic for life.
   • Despite high levels of viremia, they do not develop AIDS-like symptoms, indicating a natural tolerance to the virus.

Diagnosis:

HIV-1 and HIV-2:

• Serological tests:
  • ELISA and Western Blot are used to detect antibodies to HIV.
  • Rapid diagnostic tests (e.g., oral swabs or finger pricks) provide quicker results.
• Nucleic acid tests (PCR) detect viral RNA in blood, especially useful during acute infection when antibodies have not yet formed.
• CD4+ T-cell count and viral load tests are used to monitor disease progression and effectiveness of treatment.

SIV:

• In non-human primates, antibody-based tests and PCR are used to diagnose SIV infection.
• SIV infection in wild primates is typically identified during research or in captivity.

Control and Prevention:

HIV:

• Antiretroviral therapy (ART): There is no cure, but ART helps control HIV replication and prevent progression to AIDS.
  • ART also reduces viral load to undetectable levels, significantly lowering the risk of transmission.
• Preventive measures include:
  • Condom use during sex to prevent sexual transmission.
  • Pre-exposure prophylaxis (PrEP) and Post-exposure prophylaxis (PEP) for high-risk individuals.
  • Needle exchange programs to reduce the spread through contaminated needles.
  • Prevention of mother-to-child transmission via ART during pregnancy and avoiding breastfeeding.

SIV:

• There is no treatment for SIV in non-human primates, but understanding the virus’s interaction with its natural hosts offers insight into HIV pathogenesis and potential treatments.
• Preventive research is primarily focused on animal studies to develop vaccines and better understanding of immune response mechanisms.

Disease Impact:

HIV in Humans:

• HIV/AIDS has been a global pandemic, with tens of millions of deaths since its emergence in the 1980s.
• Despite the availability of life-saving ART, over 38 million people globally live with HIV, and it disproportionately affects populations in Sub-Saharan Africa.
• HIV also carries significant social stigma and has far-reaching social and economic impacts.

SIV in Primates:

• In natural hosts, SIV causes little to no disease, which has made these species valuable in HIV research to understand how long-term infection without progression to AIDS is possible.
• In non-natural hosts (e.g., rhesus macaques), SIV can cause simian AIDS, serving as an essential model for studying HIV in humans.

Immune Response and Viral Persistence:

• Primate lentiviruses establish lifelong infections due to their ability to integrate into the host's genome (as a retrovirus) and evade the immune system through high antigenic variation and latency.
• The immune system is unable to clear the virus, leading to persistent infection and, eventually, severe immune depletion (in the case of pathogenic infections).
• The viral reservoir, particularly in latent infection in CD4+ T-cells, makes eradication of HIV extremely challenging.

Management of Infected Individuals:

HIV in Humans:

• ART: Lifelong adherence to ART is essential for controlling HIV and preventing progression to AIDS.
• Monitoring: Regular CD4+ counts and viral load tests help track disease progression and treatment effectiveness.
• Preventing opportunistic infections through vaccinations, prophylactic antibiotics, and prompt treatment of infections is critical for maintaining the health of HIV-positive individuals.

SIV in Non-Human Primates:

• In captive settings, animals infected with pathogenic SIV are managed similarly to HIV-positive patients, focusing on preventing opportunistic infections.
• SIV in natural hosts requires minimal intervention due to the absence of disease symptoms.

Primate lentiviruses, particularly HIV, represent one of the most significant public health challenges in modern times, while SIV in non-human primates continues to offer invaluable insights into understanding viral persistence, immune evasion, and potential avenues for therapy and vaccine development.

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