Lecture 7 - HIV Pathogenesis - Virology

I. History and Magnitude

• First Documented Cases (Early 1980s):

  • Men with a rare form of cancer presenting lesions (Kaposi Sarcoma) around the neck, back, and mouth.

  • Men suffering from Pneumocystis pneumonia, a serious lung infection caused by a fungus.

  • Emergence of new diseases targeting immunocompromised populations.

Fears and Misconceptions

• AIDS stands for Acquired Immune Deficiency Syndrome.

• Transmission routes include:

  • Birth (from mother to child)

  • Heterosexual contact

  • Sharing needles (intravenous drug use)

Current Global Statistics

• Infection and Mortality Rates:

  • New HIV infections every 12 seconds.

  • Deaths from AIDS every 16 seconds.

  • Approximately 39 million people currently living with HIV/AIDS globally.

  • 30 million people have died from AIDS-related causes.

• Comparative Scale: AIDS has impacted global populations more significantly than many wars.

HIV/AIDS as a Global Phenomenon

Statistics in Sub-Saharan Africa

• About 24 million total infections.

• Annual New Infections: 2 million new cases yearly.

• Annual Death Toll: 1.2 million deaths.

Number of Infected Patients Receiving Therapy

Antiretroviral Therapy (CART)

• Combined Antiretroviral Therapy: Used to manage and treat HIV.

  • if you stop taking the meds then the virus will start propagating very fast

• Distribution of Patients by Region (Total: 9.7 million receiving therapy):

  • African Region: 7.53 million

  • Region of the Americas: 308,000

  • South-East Asia Region: 25,100

  • European Region: 199,000

  • Eastern Mediterranean Region: 938,000

  • Western Pacific Region: 722,000

  • High-income countries: 199,000

Increase in Therapy

Contributions of Mark Wainberg

• Renowned Canadian scientist (1945-2017) and past president of the International AIDS Society.

• Promoted annual AIDS meeting in South Africa since 2000, significantly impacting global awareness and treatment progress.

• diseases and perseverance of diseases often correlate with income

HIV Virology

Introduction to HIV

• HIV (Human Immunodeficiency Virus) is the cause of AIDS.

• Part of the retrovirus family (Retroviridae) and the subfamily Lentiviruses.

• Human Infecting Viruses: HIV-1 and HIV-2.

Reverse Transcriptase Activity

• Enzyme that converts viral RNA into DNA, facilitating integration into host genomes.

• Key Concepts:

  • ssDNA cannot be transcribed.

  • Cellular DNA polymerase is crucial for synthesizing double-stranded DNA.

HIV Structural Proteins

• Key proteins identified by molecular weight and glycosylation:

  • SU (Surface Unit) as gp120: Viral receptor.

  • TM (Transmembrane) as gp41: Fusion protein.

  • CA (Capsid) as p24: Core structural protein.

Life Cycle of Retrovirus

• Integration of double-stranded viral DNA into host genome, forming a pre-initiation complex (PIC).

HIV Origins and Diversity

Historical Presence in Africa

• Evidence of HIV dating back to 1959 from archived samples in Zaire (Central Africa).

• High prevalence in urban sex workers in major cities of Zaire and Rwanda.

Group Diversity

• Based on sequence alignments, the major groups include:

  • Group M: Major global form, highly prevalent.

  • Group N and O: Potential transfer from animals to humans resulting in distinct strains.

• Diversity in HIV-1: Multiple subtypes based on geographical prevalence.

HIV Transmission Sources

• Primary Source: Close resemblance of HIV-1 to SIV (Simian Immunodeficiency Virus) found in chimpanzees (SIV cpz).

• Transmission dynamics:

  • SIV primarily transmitted through sexual contact among infected chimps.

  • Contact with SIV-positive monkeys likely facilitated cross-species transmission to humans.

• origin of virus is central africa

• SIV in chimps is excreted in feces

  • chimps can’t swim

  • This mode of transmission highlights the ecological factors that contributed to the emergence of HIV in human populations.

    • tend to concentrate in one area bcs they are in isolated areas

    • HIV = exogenous retrovirous… comes from a source

    • endogenous retroviruses translate through the germline

HIV Transmission

Mechanisms Leading to Outbreaks

• Transmission events linked to bushmeat hunting activities in the early 1920s, notably around Kinshasa, Zaire.

• Factors influencing outbreaks:

  • Urbanization during European colonization.

  • Sex work as a transmission route.

  • The introduction of modern healthcare in African regions.

• Virus Characteristics:

  • Conditions required for successful transmission appear limited due to inherent weaknesses of the virus under various environmental factors.

Conclusion

• Understanding HIV pathogenesis is crucial for combating the epidemic, focusing on history, transmission, and current treatment strategies.