Virology Ch.29 HIV

Human Immunodeficiency Virus (HIV)

  • Virion Characteristics

    • Spherical enveloped particle
    • Diameter: 100 nm
    • Conical capsid
    • Genome:
    • Linear single-stranded RNA, positive sense
    • Length: 9.3 kb
    • Contains two identical genome RNAs in each virion
    • Cellular tRNAlys3 molecules packaged in virions used as primers for reverse transcription

  • Genes and Proteins

    • Capsid Proteins:
    • Matrix (MA)
    • Capsid (CA)
    • Nucleocapsid (NC)
    • p6
    • Enzymes:
    • Protease (PR)
    • Reverse Transcriptase (RT)
    • Integrase (IN)
    • Envelope Proteins:
    • Surface (SU)
    • Transmembrane (TM)
    • Regulatory Proteins:
    • Vif, Vpu, Vpr, Tat, Rev, Nef

HIV and its Hosts

  • Classification:
    • HIV is a lentivirus originating from the Latin "lentis" meaning slow, reflecting the slow disease progression
    • Types of HIV:
    • HIV-1 (more prevalent)
    • HIV-2
    • Related viruses:
    • Simian Immunodeficiency Virus (SIV)
    • Equine, Bovine, Feline Immunodeficiency Viruses

Historical Context

  • 1981: Emergence of AIDS epidemic
  • 1983: Identification of HIV as the causative agent
    • Key researchers include Barre-Sinoussi, Chermann, and Montagnier
    • 2008: Nobel Prize awarded to F. Barre-Sinoussi and L. Montagnier for their discovery

HIV/AIDS Impact

  • Pandemic Scope:

    • Over 36 million people infected globally

  • Pathogenic Mechanism:

    • HIV replicates in and destroys lymphocytes, particularly CD4+ T cells, impairing immune function
    • Opportunistic infections due to compromised immunity can be fatal
    • Transmission occurs through sexual contact and blood exchange

Disease Progression

  • Phases of HIV Infection:

    1. Acute Phase:
    • Mononucleosis or flu-like symptoms within 2-6 weeks
    • Infection leads to CD4+ T cell depletion in Gut-Associated Lymphoid Tissue (GALT)
    1. Clinical Latency:
    • Gradual CD4+ T cell depletion continues
    1. AIDS:
    • Marked by high viral loads; symptoms include chronic fever, night sweats, and susceptibility to opportunistic infections

  • Progressors:

    • Rapid progressors (10-15%): develop late-stage symptoms in 2-3 years
    • Slow progressors (70-80%): develop late-stage symptoms in 8-10 years
    • Long-term non-progressors (5%): stable CD4+ levels

Treatment Possibilities

  • Antiviral Treatments:
    • Control HIV-1 infection and disease progression
    • Combinations of drugs targeting reverse transcriptase and protease have been effective
    • No current effective vaccine available

Distinctive Characteristics of HIV-1

  • Targeting Mechanism:

    • HIV-1 specifically targets CD4+ T cells and macrophages through CD4 antigens and co-receptors (CCR5 or CXCR4)

  • Viral Entry Mechanism:

    • Utilizes gp120 for CD4 binding and co-receptor interactions leading to fusion via gp41

  • Latency Challenges:

    • HIV integrates its DNA leading to latency, complicating elimination efforts
    • Transcriptional controls allow for periods of quiet while maintaining infection

Gene Function Overview

  • Tat Protein:
    • Increases transcription by promoting elongation by RNA polymerase II
  • Rev Protein:
    • Mediates transport of viral mRNAs to the cytoplasm
  • Vif Protein:
    • Enhances viral infectivity by inhibiting host defenses
  • Vpr Protein:
    • Facilitates viral replication and transport into the nucleus
  • Vpu Protein:
    • Promotes the release of new virions from infected cells
  • Nef Protein:
    • Modulates immune response and enhances viral replication

Conclusion

  • HIV-1's Complexity:
    • HIV-1's rapid mutation rate and ability to establish latency present significant challenges for treatment and cure. The virus employs multiple auxiliary proteins to navigate immune defenses and facilitate replication, highlighting the complexity of HIV-1 pathogenesis and the importance of ongoing research in managing this global health issue.