RETROVIRUSES

• What are retroviruses?

  ssRNA viruses that replicate through a DNA intermediate using reverse transcriptase
• Retroviruses are associated with cancers, leukemias and the AIDS syndrome, and cause degenerative and neurological syndromes
• Retroviruses penetrate either by fusion with the PM, or via endocytosis

  -Integration is essential for productive infection

  -transfer of DNA to nucleus happens during cell division (simple retroviruses), when nuclear envelope is disassembled

  -Provirus is stable; no mechanism for precise excision is known; integration is essentially irreversible
• (HIV) is a lentivirus (slowly replicating complex retrovirus) that causes the acquired immunodeficiency syndrome (AIDS).
• Life cycle of HIV:

  A) gp120

  B) CD4

  C) CXCR4

  D) CCR5

  
• life cycle of HIV: Fusion; Viral envelope fuses with cell membrane (gp41), releasing contents into the cell
• Life cycle of HIV: replication; Viral RNA is converted into DNA by reverse transcriptase, Viral DNA is inserted into host cell chromosome by enzyme integrase. Integrated viral DNA may remain latent for years and is called a provirus., Viral DNA is transcribed and RNA is translated, making viral proteins. Viral genome is replicated.
• HIV proteins:

  A) gag

  B) vif

  C) env

  D) LTR

  E) LTR

  F) pol

  G) vpr

  H) rev

  I) nef

  J) vpu

  K) tat

  
• Lifespan of HIV:

  A) primary infection

  B) acute HIV infection

  C) Anti-HIV immune response

  D) CD4 T-cells

  E) HIV rna

  
• Symptoms/ cause of death in Late AIDS:

  • Diarrhea
  • Wasting (extreme weight loss)
  • Abdominal pain
  • Infections of the mouth and esophagus- Pathogens:  Candida albicans, cytomegalovirus, Microsporidia, and Cryptosporidia.
• Drugs against HIV:

  • Nucleoside RT inhibitors (NRTI) and Nucleotide RT inhibitors (NtRTI) both act as competitive substrate inhibitors
  • Non-Nucleoside RT inhibitors (NNRTI) act as RT inhibitors
  • Integrase inhibitors (INSTI)
  • Protease inhibitors (PI)
• Treatments against HIV:

  • anti-retroviral therapy (ART)
  • combination anti-retroviral therapy (cART)
  • highly active anti-retroviral therapy (HAART)
  • Typical combinations of most current HAART regimens consist of three drugs:  2 NRTIs as a "backbone" + a PI/NNRTI/INSTI as a “base”
• Anti- retroviral therapy: ART does not cure HIV infection but suppresses viral replication within a body and allows an individual's immune system to strengthen and regain the capacity to fight off infections.