Basics of HIV Virus Vijay Kandula, MD MPH AAHIVS Adjunct Assistant Professor Division of Public Health, Department of Family and Preventive Medicine University of Utah, Salt Lake City 2013

Viruses are not living organisms Viruses do not Grow Metabolize Viruses do Infect cells and use the host cell to make more copies of themselves Cause disease in many organisms

Parts of a Virion (a virus particle) Nucleic Acid – RNA or DNA Capsid – protein coat that surrounds the DNA or RNA in a virus Lipid Membrane – a membrane around the capsid in many kinds of viruses; helps the virus enter cells (“enveloped” viruses; without the membrane, the virus is “naked”) Made of proteins, lipids, and glycoproteins

Mutating viruses Viruses can mutate when they copy the genetic material For e.g., a photocopy of document with stains; they show up in subsequent copies Mistake proves useful Can lead to stronger virus (more infectious) Viruses don’t mutate often, except… Influenza HIV

Produces 1010-1012 new virions each day HIV Replication RNA Virus Produces 1010-1012 new virions each day

Basic Structure Viral envelope: lipid layer; glycoproteins protrude from surface Glycoproteins enable virus to recognize surface proteins of special CD4 or T Helper Cells (a special type of immune cells) This allow entry into these cells (like a key to the cell’s door) 2 strands/copes of RNA only 9 genes; 3 are found in many viruses (structural proteins) Reverse Transcriptase enzyme converts RNA into DNA (this makes HIV a RETROvirus); This DNA instructs cell to make more viruses

The first step of infection is the binding of gp120 to the CD4 receptor of the cell, which is followed by penetration and uncoating. The RNA genome is then reverse transcribed into a DNA provirus which is integrated into the cell genome. This is followed by the synthesis and maturation of virus progeny.

HIV Replication 3D Medical Animation http://www.youtube.com/watch?v=9leO28ydyfU

Introduction Continued

Introduction Continued

Introduction Continued

HIV Types, Groups, and Subtypes There are 3 HIV-1 genotypes; M (Main), O (Outlayer), and N (New) and P (New) M group comprises of a large number subtypes and recombinant forms Subtypes - (A, A2, B, C, D, F1, F2, G, H, J and K) Recombinant forms - AE, AG, AB, DF, BC, CD O, N and P group subtypes not clearly defined, especially since there are so few N and P group isolates. As yet, different HIV-1 genotypes are not associated with different courses of disease nor response to antiviral therapy. However, certain subgroups may be difficult to detect by certain commercial assays.

Geographic Distribution of HIV-1 Subtypes and HIV-2 A,B,A/B B B HIV-2 C,E C HIV-2 EB C A,G,A/G A,D BFC C B Subtypes A, B, C, D, “E”, F, G, H, “I”, J, K, CRFs, and untypable

HIV half-lives Activated cells that become infected with HIV produce virus immediately and die within one to two days. Production of virus by short-lived, activated cells accounts for the vast majority of virus present in the plasma. The time required to complete a single HIV life-cycle is approximately 1.5 days. Resting cells that become infected produce virus only after immune stimulation; these cells have a half-life of at least 5-6 months. Such long-lived cell populations present a major challenge for anti-retroviral therapy.

HIV Origins

HIV Origins

HIV Evolution Selection Pressure

HIV Evolution Types of selection pressure that effects HIV Immune selection Antiretroviral Treatment