HIV-1 Infection: Molecular Biology, Global Impact, and Therapy, Exams of Molecular biology

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TRACO

Frank Maldarelli

HIV Dynamics and Replication Program

NCI

Retroviruses

Retroviruses

• Introduction
• Molecular Biology/Replication
• Retroviruses in Human Populations
• Emergence/Spread
• HIV Therapy and Beyond
• Lessons

UNAIDS, On Therapy 38, On Therapy: 2.1 million On Therapy: 320, On Therapy: 1.8 million On Therapy: 10.2 million On Therapy: 1.4 million On Therapy: 1.1 million Global Burden of HIV-1 Infection People undergoing antiretroviral therapy: 17 million

The Need is Great

Office of AIDS research

Retroviruses A group of RNA viruses that replicate via a DNA intermediate using Reverse Transcriptase.

Retrovirus classification

Lentivirus Relationships HIV- 2 SIV-smm SIV-syk HIV- 1 SIV-cpz SIV-agm VMV CAEV EIAV BIV FIV SIV-mnd 1 % difference

Retrovirus conventions

Retroviruses Glossary

• gag: group antigen
• pol: polymerase
• env: envelope
• tat: Transactivator
• rev:Regulator of Expression of Virion proteins - U3: unique sequence in 3ʼ region - U5: Unique sequence in 5ʼ region - R: Repeat sequence - PBS Primer binding site for initiation of RT - Ppt: polypurine tract primer for RT - TAR: Tat activating sequence - RRE: Rev responsive element - Provirus: copy of retrovirus that is integrated into host genome

HIV replication

HIV Attachment and Entry

• Virus Factors
  • Attachment: Env glycoprotein gp
  • Entry: Env glycoprotein gp
• Host Cell Factors
  • Receptor
    • CD
  • Co-receptor (major)
    • CXCR
    • CCR

Blocking the HIV coreceptor

Blocking HIV Fusion