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    Human Immunodeficiency Virus Lecture

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    api-19969058
    This document summarizes key aspects of HIV including its structure, genes, transmission, pathogenesis, clinical stages, opportunistic infections, and laboratory diagnosis. It describes HIV as a retrovirus that causes AIDS by infecting CD4+ T cells and macrophages. The virus contains RNA, reverse transcriptase, integrase, and protease enzymes. It is transmitted sexually or through blood and can progress from acute infection to clinical latency to late stage AIDS defined by low CD4 counts and opportunistic infections. Laboratory diagnosis involves antibody, antigen, nucleic acid, and viral isolation tests.

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    Human Immunodeficiency Virus Lecture

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    api-19969058
    105 views34 pages
    This document summarizes key aspects of HIV including its structure, genes, transmission, pathogenesis, clinical stages, opportunistic infections, and laboratory diagnosis. It describes HIV as a retrovirus that causes AIDS by infecting CD4+ T cells and macrophages. The virus contains RNA, reverse transcriptase, integrase, and protease enzymes. It is transmitted sexually or through blood and can progress from acute infection to clinical latency to late stage AIDS defined by low CD4 counts and opportunistic infections. Laboratory diagnosis involves antibody, antigen, nucleic acid, and viral isolation tests.

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    Human immunodeficiency virus lecture

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    This document summarizes key aspects of HIV including its structure, genes, transmission, pathogenesis, clinical stages, opportunistic infections, and laboratory diagnosis. It describes HIV as a retrovirus that causes AIDS by infecting CD4+ T cells and macrophages. The virus contains RNA, reverse transcriptase, integrase, and protease enzymes. It is transmitted sexually or through blood and can progress from acute infection to clinical latency to late stage AIDS defined by low CD4 counts and opportunistic infections. Laboratory diagnosis involves antibody, antigen, nucleic acid, and viral isolation tests.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    105 views34 pages

    Human Immunodeficiency Virus Lecture

    Uploaded by

    api-19969058
    This document summarizes key aspects of HIV including its structure, genes, transmission, pathogenesis, clinical stages, opportunistic infections, and laboratory diagnosis. It describes HIV as a retrovirus that causes AIDS by infecting CD4+ T cells and macrophages. The virus contains RNA, reverse transcriptase, integrase, and protease enzymes. It is transmitted sexually or through blood and can progress from acute infection to clinical latency to late stage AIDS defined by low CD4 counts and opportunistic infections. Laboratory diagnosis involves antibody, antigen, nucleic acid, and viral isolation tests.

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    Human immunodeficiency

    virus
    (HIV)
    HIV is the cause of acquired
    immune deficiency
    syndrome (AIDS)
    Characteristics of the virus

    • Is a single stranded, diploid RNA, enveloped virus


    of the lentivirus subfamily of retroviruses.
    • The reverse transcriptase makes copies of DNA
    from the viral RNA.
    Characteristics of the virus

    • Outer envelope contains a lipid matrix within which


    specific viral glycoproteins are imbedded.
    • These knob-like structures responsible for binding
    to target cell.
    Human immunodeficiency virus
    Structural Genes

    • Group Specific Antigen (Gag)- encodes


    core protein (p24) & matrix protein (p17).
    • Envelope (Env)- encodes gp160, cleaved
    into gp120 & gp41.
    • Polymerase (Pol)- encodes reverse
    transcriptase, protease & integrase
    enzyme.
    Group Specific Antigen (Gag)

    • Gag gene encodes for nucelocapsid & matrix


    protein of virus.
    • Neocleocapsid protein (p24) used in serological
    test.
    • p17 lies between protein core and envelope.
    Envelope (Env)

    • Envelope (Env) gene codes for envelope protein


    gp160 will eventually be cleaved by proteases to
    gp120 and gp41.
    • The gp120 binds specifically to CD4 receptor on
    host cell, mutates rapidly & results in antigenic
    variation.
    • Gp41 causes fusion of the virus to the cell
    membrane & virus particle enters cell.
    Polymerase (Pol)

    • Polymerase (Pol) codes for reverse


    transcriptase, protease & integrase enzyme.
    • Located in the core, close to nucleic acids.
    • Responsible for conversion of viral RNA into
    DNA, integration of DNA into host cell DNA and
    cleavage of protein precursors.
    Important enzymes

    • Reverse Transcriptase (RT) – converts RNA


    genome into a DNA copy
    • Integrase (IN) – inserts the DNA copy into
    host genome
    • Protease (PR) – Cuts and processes
    immature HIV proteins into mature,
    functioning proteins
    Methods of transmission

    • Sexually, presence of STD increases transmission.


    • Exposure to infected blood or blood products.
    • Sharing contaminated needles.
    • Transplantation of infected tissues or organs.
    • Mother to fetus, perinatal transmission variable,
    dependent on viral load and mother’s
    CD 4 count.
    Methods of transmission

    • HIV has been found in saliva and tears in very low


    quantities from AIDS patients, but has never been
    shown to result in transmission of HIV.
    • Researchers at CDC and elsewhere have shown
    no evidence of HIV transmission through
    insects.
    Pathogenesis

    • First step, HIV attaches by gp120 to the CD4


    antigen found on a variety of cells-
    ● helper T cells ● macrophages ● monocytes
    ● B cells ● microglial brain cells
    ● T cells infected later on.
    Pathogenesis

    • In early phase HIV infection,


    viruses are M-tropic.
    • Their gp120 is able to bind to
    CD4 molecule and
    chemokine receptors called
    CCR5 found on
    macrophages
    Pathogenesis

    • In late most of the viruses are


    T-tropic,
    • Having gp120 capable of
    binding to CD4 and CXCR4
    found on T4-lymphocytes.
    Clinical findings

    • Clinical features occur in three stages:


    • Acute stage
    • Latent stage
    • Late, immunodeficiency stage
    Acute symptoms

    • Mononucleosis-like, cold or flu-like symptoms


    may occur 2 to 4 weeks after infection.
    – Fever, sore throat, Lymphadenopathy,
    Rash, headache, Fatigue or
    no symptoms may be present
    Window period

    • Antibody appears 3-4 wks after infection with HIV, before


    antibody is detected the patient is serologically “false
    negative” for HIV infection.
    • Patient is highly infectious,
    • Lab diagnosis during window period-
    • P24 antigen assay
    • Viral Culture
    • PCR
    Clinical Latency Period

    • After initial viremia, a viral set point (viral load)


    occurs.
    • Patient is asymptomatic at this period.
    • Though the patient is asymptomatic viral replication
    occurs.
    Late stage

    • CD4 count gradually declines from its normal value


    of 500-1200.
    • Once CD4 count drops below 200/μl, infected
    person is considered to have advanced HIV
    disease & at risk for opportunistic infections
    and malignancy.
    AIDS

    • In late stage neurological problem e.g.


    dementia and neuropathy develops
    – Most deaths occur with CD4 counts
    below 50.
    Opportunistic Infections

    • Respiratory system ● Central/peripheral Nervous system


    – Pneumocystis Carinii - Cytomegolavirus
    Pneumonia. - Toxoplasmosis
    – Tuberculosis - Cryptococcosis
    – Kaposi's Sarcoma - Non Hodgkin's lymphoma
    • Gastro-intestinal system - Varicella Zoster
    – Cryptosporidiosis - Herpes simplex
    – Candida ● Skin
    – Cytomegolavirus - Herpes simple
    – Isosporiasis - Kaposi's sarcoma
    – Kaposi's Sarcoma - Varicella Zoster
    Oral Candidiasis (thrush)
    Oral Hairy Leukoplakia
    Kaposi’s sarcoma (KS)

    • Kaposi’s sarcoma is a rare


    cancer of the blood vessels
    that is associated with HIV.
    It manifests as bluish-red
    oval-shaped patches that
    may eventually become
    thickened. Lesions may
    appear singly or in clusters.
    Laboratory Diagnosis of HIV Infection

    • Antibody detection
    • Antigen detection
    • Detection of viral nucleic acid
    • Viral isolation
    • Indirect predictors of HIV infection
    Three types of tests

    (i) Screening tests - ELISA and simple/rapid tests.


    (ii) Confirmatory- Western Blot assay.
    (iii) Nucleic acid based tests- Polymerase chain
    reaction (PCR).
    ELISA Test

    • Antibodies detected in ELISA against: p24,


    gp120, gp160 and gp41 antigen.
    • ELISAs are for screening only
    • False positives occur in alcoholism,
    syphilis, and immunoproliferative diseases.
    Other Screening Tests

    • Agglutination tests: Latex particles, Gelatin


    particles and
    • Comb-dipstick based systems
    • Dot-Blot Test: A rapid, cost-effective.
    • Most have sensitivities and specificities of
    99% and 98% respectively
    Rapid Tests

    • Advantages:
    – quicker to perform
    – do not require specialised equipment or trained
    personnel
    Western Blot

    • Most popular confirmatory test.


    • Antibodies to p24 and p55 appear earliest but
    decrease or become undetectable.
    • Antibodies to gp31, gp41, gp 120, and gp160
    appear later but are present throughout
    all stages of the disease.
    Indirect immunofluorescence

    Can be used to detect both virus and antibody to it.


    •
    Viral Load Tests

    • Viral load is the quantity of HIV-RNA in the blood.


    • Viral load tests measure the amount of HIV-RNA in
    one milliliter of blood.
    Issues in Testing

     HIV antibody testing and


    counseling should always be
    voluntary and confidential.

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