HIV Structure and Characteristics

HIV Introduction

• HIV is a viral infection that destroys helper T cells of the immune system
• HIV is a lentivirus, belonging to the genus of the retroviridae family
• Characterized by long incubation periods and persistent infection
• Infects a wide range of primate hosts, as well as some non-primate mammals

Morphology

• Icosahedral (20-sided) shape
• Retroviruses transcribe RNA to DNA
• Two viral strands of RNA found in the core, surrounded by a protein outer coat
• Enveloped virus with a lipid matrix containing specific viral glycoproteins
• gp120 (wedge-shaped) and gp41 (knob-like) structures responsible for binding to target cells

Types of HIV

• Two species of HIV infect humans: HIV-1 and HIV-2
• HIV-1 is more virulent, relatively easy to transmit, and accounts for the majority of HIV infections globally
• HIV-2 is less transmittable and largely confined to West Africa

Origins of HIV

• HIV-1 likely descended from SIVcpz (Simian Immunodeficiency Virus of chimpanzees)
• HIV-2 likely descended from SIVsm (Simian Immunodeficiency Virus of sooty mangabeys)

History

• 1926-1946: Scientists believe HIV first spread from monkeys to humans
• 1959: First proven AIDS death
• 1978: Gay men in the US and Sweden begin showing signs of what is now known as AIDS
• 1981: CDC notices an increase in cases of Kaposi’s sarcoma and Pneumocystis carinii pneumonia
• 1982: The term AIDS (Acquired Immune Deficiency Syndrome) is used for the first time
• 1983: Institute Pasteur isolates HIV-1; CDC issues warning to blood banks about potential problem
• 1984: Dr. Robert Gallo claims discovery of HIV

Epidemiology

• The virus was first successfully identified and classified in 1981
• By the end of 2003, 1,039,000 to 1,185,000 persons were infected with HIV/AIDS in the US
• Global statistics (2006): 39.5 million infected with HIV/AIDS, with 4.3 million new infections
• 2.8 million (65%) of these new infections were in sub-Saharan Africa
• Increases in Eastern Europe and Central Asia, with a more than 50% rise in infection rates since 2004
• 2.9 million deaths due to AIDS-related illnesses in 2006

Transmission

• Sharing of infected drug injection needles/syringes
• Accidental needle stick (healthcare professionals)
• Unprotected sex with infected individual
• Blood transfusions/Organ transplants
• Transmission from infected mother-to-fetus during pregnancy or delivery
• Transmission from breast milk of infected mother to her baby

Pathogenesis and Virulence Factors

• HIV enters through mucous membrane or skin and travels to dendritic phagocytes beneath the epithelium, multiplies, and is shed
• Virus is taken up and amplified by macrophages in the skin, lymph organs, bone marrow, and blood
• HIV attaches to CD4 and coreceptor; HIV fuses with cell membrane
• Reverse transcriptase makes a DNA copy of RNA
• Viral DNA is integrated into host chromosome
• Can produce a lytic infection or remain latent

Primary and Secondary Effects of HIV Infection

• Primary effects: extreme leukopenia, formation of giant T cells, and infected macrophages releasing the virus in the central nervous system
• Secondary effects: destruction of CD4 lymphocytes, allowing for opportunistic infections and malignancies

Clinical Manifestations

• Human Immunodeficiency Virus (HIV) has an incubation period of about 10 years and eventually leads to Acquired Immunodeficiency Syndrome (AIDS)
• AIDS results in the impairment of the immune system, leading to death from infections, secondary diseases, or many different types of cancers
• Common diseases associated with HIV infection: Kaposi's sarcoma (KS), Pneumocystis carinii pneumonia (PCP), and Mycobacterium avium complex (MAC)

Laboratory Tests

• Methods utilized to detect: Antibody, Antigen, Viral nucleic acid, and Virus in culture
• ELISA testing: detects antibodies directed against p24, gp120, gp160, and gp41
• Western Blot: utilizes a lysate prepared from HIV virus to separate out HIV proteins (antigens)
• Indirect immunofluorescence: detects both virus and antibody to it
• PCR: looks for HIV DNA in the WBCs of a person
• Virus isolation: used to definitively diagnose HIV

Prevention and Treatment

• Prevention: avoid sexual contact with infected individuals, avoid sharing needles/syringes, avoid contact with bodily fluids
• New methods for prevention: intravaginal lime or lemon juice, intravaginal oestrogen, male circumcision, and post-coital penile hygiene
• Treatment: anti-viral agents, Nucleoside Reverse Transcriptase inhibitors (e.g., AZT), Non-Nucleoside Transcriptase inhibitors (e.g., Viramune), and Protease inhibitors (e.g., Norvir)
• Vaccine: currently, no vaccines are approved for use by the FDA; two types in development: therapeutic vaccine and preventive vaccine