HIV + AIDS

HIV + AIDS

1. ORIGIN + ITS VARIATION

   • Today (2012)
     • Data from World Health Organisation Highest in Sub-Saharan Africa (25 million) Then S+S.E. Asia
     • Total adults+children estimated living with HIV : 35.3 million
     • Children <15: 3.3 million
       • Especially severe More skewed Less Mother-&gt;child transmission via blood delivery Drugs required before + after delivery - more available in developed countries
     • Newly infected with HIV : 2.3 million
   • PRIMATES
     • Simian Immunodeficiency Virus (SIVs)
       • In natural hosts, often non-pathogenic
     • Chimpanzee
       • SIVcpz -> HIV-1 M
     • Gorilla
       • SIVgor -> HIV-1 O
         • From chimpanzee -&gt; gorilla -&gt; human
     • Sooty Mangaby
       • SIVsm -> HIV-2
         • From "pets" to humans again
     • How do jumps occur?
       • Genetic similarity
         • Phylogenetic tree of HIVs + SIVs based on sequencing data
       • Cut Hunter Theory
         • SIVcpz transmission by direct exposure to infected animal blood - BUSH MEAT
           • Viral spread favoured by social, economic + behavioural changs in early 20th century
         • Today: Simian Foamy Virus, Camaroon
   • WHEN?
     • HIV-1 origin: 1912
       • range: 1920-1935
     • 1st available virus isolate: 1952 (Kinshasa)
     • 1st HIV-1 seroconversion (infection): 1959 (Kinshasa)
       • Seroconversion = &nbsp;development of detectable specific&nbsp;antibodies&nbsp;to&nbsp;microorganisms&nbsp;in the&nbsp;blood serum&nbsp;as a result of&nbsp;infection&nbsp;or&nbsp;immunization.
     • 1st 5 reported cases of AIDS: 1981 (USA)
     • No. deaths directly due to AIDS 2007: >24 million
     • No. people infected with HIV-1 2008: ~33 million
     • epidemic: 1908
       • From samples (1960) recovered from hospital in Congo
   • VARIATION
     • Group M
       • &gt;90% of cases Further divided into subtypes A-K
       • "MAJOR" worldwide
     • Group N
       • Discovered in 1998 only in Cameroon
       • "NEW"
     • Group O
       • "OUTLIER" West Central Africa
     • increasing travel -> subtype distribution changing. Potential for mixed or superinfections
       • i.e. HIV-infected individual becoming infected with another strain -&gt; viral recombination e.g. circulating recombinant forms (CRF)

2. HIV LIFE CYCLE

   • STRUCTURE
     • Viral envelope
       • Lipid bilayer
     • Env proteins
       • Protruding from envelope Heterodimers of SU3TM3
     • Gag proteins
       • Inside envelope
     • p17 proteins
       • between envelope and core
     • Viral Core
       • Contains 2000 copies of viral protein p24 Each p24 surrounds 2 single strands of HIV RNA Each RNA contains copy of HIV'S 9 genes 3 of these: gag, pol, env - encode info to make structural proteins for new virions
     • GENETIC MAP
       • Long Terminal Repeats
         • promote transcription
       • group specific antigen proteins
       • virion infectivity factor
       • polymerase
         • protease, reverse transcriptase, integrase
       • vpr
         • weak transcriptional factor
         • NUCLEAR LOCALISATION SIGNAL
       • rev
         • regulator virion proteins: promote export of viral RNAs from nucleus TRANSACTIVATING
       • tat
         • transactivator protein: regulates viral transcription
       • env
         • type-specific envelope proteins
       • vpu
         • required for efficient budding
       • nef
         • negative regulatory factor: important for virulence
   • RETROVIRUS
     • Composed of RNA Uses REVERSE TRANSCRIPTASE to convert RNA -&gt; DNA (encoded by pol) Belongs to LENTIVIRUS (slow virus - delay in onset of symptoms)
     • lentivirus (slow virus) - late onset of symptoms

3. HIV-1 INFECTION

   • CD8+T cells produced -> reduce viral load -> neutalising antibodies too -> BUT 10E10 virus particles + 10E9 infected T cells -> CD4+ T cells reduce and HIV load increases -> lymphoproliferation-associated immune system weakens -> canot replace lost T cells -> fall in CD4+ T cell increases more rapidly

4. VIRAL RESERVOIRS + LATENCY

5. ANTIRETROVIRALS

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