• endogenous (HERV)
• exogenous

• transmitted via germ cell line
• prevelance
  • most are defective, containing nonsense mutations or major deletions
  • some maintained as active genes
  • thousands in human genome

• HERV-FD
  • syncytin 2 maintained as functional cellular gene in all primates
  • role in placental morphogenesis?
• HERV-K (HML2) family
  • some have open reading frames for all viral proteins
  • HERV gene expression in several cancers (breast cancer, melanomas, teratocarcinomas)

• acquired via sexual contact, blood/body fluid exposure
• classification
  • deltaretroviruses: HTLV1, HTLV2
  • lentiretroviruses: HIV1, HIV2

• enveloped viruses (bud from host)
• two identical copies of + sense RNA
  • gag- core proteins, structural components
  • pol- protease, polymerase, integrase
  • env- envelope glycoproteins
  • LTR
    • regulatory sequence at the end of each genome
    • allow integration into host chromosome
    • controls gene expression

• via RNA dependent DNA polymerase (reverse transcriptase)
• DNA copy may translocate to the nucleus and integrate into host cell genome
• transcriptioni mediated by cellular transcriptional machinary
• viral genome will also code for factors that regulate gene expression
  • HTLV: tax, rex
  • HIV: tat, rev

• both lentiretroviruses and deltaretroviruses have a prolonged asymptomatic period
• deltaretroviruses (HTLV) have cellular transformation leading to oncogenesis
• lentiretroviruses (HIV) leads to cytopathic effects causing CD4 destruction

• non human primate lentoviruses that have crossed over
  • SIV cpz: HIV1
  • SIV sm: HIV2

• no immunopathology or clinical disease in spite of sustained viremia
  • NO absence of CD4 cells
  • lack of generalized immune activation
  • preservation of lymph node architecture
• has been cross over in Rhesus macaque
  • do develop immune dysfunction and clinical disease
  • useful animal model

• groups: M (main), N, O (outgroup)
• subgroups called clades (vary geographically and diverge from common ancestor
  • ex: group M, clade B most common in US
• circulating recombinant forms (CRF's)- different clades combine gene segments forming hybrids
  • especially seen in areas of rapid tranmission
• important determinants in vaccine design

• tat
• rev
• nef
• vif
• vpu
• vpr

• promotes nuclear export of incompletely spliced/unspliced viral RNA's

• downregulates host cell CD4 and MHC class I expression
• increases viral release from cells

• down regulates host cell CD4 expression
• increase viral release from cells

• promotes nuclear import of viral DNA
• G2 cell cycle arrest

1. attachment/fusion/entry mediated by:
   • CD4 R's: T lymphocytes, follicular dendritic cells, macrophages
   • chemokine receptors: CXCR4, CCR5
     • in general, most have specificity for either CXCR4, CCR5, but some can be dual tropic
2. reverse transcription
3. nuclear translocation
4. integration
5. transcription
   • uses cellular enzymes and controls events using HIV regulatory gene proeducts (Tat and Rev) that bind to specific HIV RNA regions
6. RNA processing
   • takes advantage of cellular enzymes
   • controled using HIV reg genes
   • reg gene products function by binding specific HIV RNA regions
   • HIV RNA can fold onto itself via base pairing
7. translation
8. assembly
9. maturation occurs after budding

• cytopathic effect: non syncytium inducing (NSI)
• cell distribution
  • macrophages
  • microglia
  • lymphocytes

• cytopathic effect- syncytium inducing
• cell distribution: lymphocytes

• origin: cross species transmission from sooty mangabey in Gabon
• 8 groups (A, B found mainly in men)
• epidemiology
  • limited to West Africa, India
• prognosis
  • lower transmission rate
  • less pathogenic with slower rate of progression
  • different drug sensitivities

• origin: simian TLV1
• 5 subtypes (high degree of nucleotide sequence conservation
  • C: worldwide, Caribean
  • J: Japanese
  • WA: West African
  • M: Melanesian

• infects wide variety of cells including CD4 cells, CD8 cells, endothelial cells, fibroblasts
• tax (transactivator)
  • activates transcription of viral and cellular genes that facilitate viral infection (ex: NFkB)
  • oncogenes
• rex (regulator of expression)
  • stabilizes mRNA for export to cytoplasm
  • favors production of structural proteins and downregulate tax

• via cell associated virus
• risk factors
  • IVDU, blood products
  • sexual transmission (esp. in women with discordant couples)
  • unlikely vertical transmission
  • breast feeding (ingestion of infected milk born lymphocytes)

• human T cell lymphoma
  • associated with bone involvement, hypercalcemia
• HTLV-1 associated myelopathy (tropical) spastic parapesis

• US, Europe, SE Asia
• Ameriindiains in North, Central and South America
  • esp. Brazil
• Pygamy tribes in Central Africa

myelopathy (tropical) spastic paraparesis