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    Human Immunodeficiency Virus

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    Malueth Angui
    HIV/AIDS was first recognized in 1981 in the US. HIV targets and destroys CD4 T cells, weakening the immune system and allowing opportunistic infections. There are two types, HIV-1 being more prevalent. It is transmitted through sexual contact, blood/blood products, and from mother to child. The virus enters cells through binding proteins on its envelope to CD4 and chemokine receptors on the target cell. It replicates by integrating into the host cell DNA. Antibodies are produced but do not neutralize the virus well. The disease progresses through acute, latent, and late stages characterized by declining CD4 counts and opportunistic infections like PCP and Kaposi's sarcoma.

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    © All Rights Reserved
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    Human Immunodeficiency Virus

    Uploaded by

    Malueth Angui
    32 views24 pages
    HIV/AIDS was first recognized in 1981 in the US. HIV targets and destroys CD4 T cells, weakening the immune system and allowing opportunistic infections. There are two types, HIV-1 being more prevalent. It is transmitted through sexual contact, blood/blood products, and from mother to child. The virus enters cells through binding proteins on its envelope to CD4 and chemokine receptors on the target cell. It replicates by integrating into the host cell DNA. Antibodies are produced but do not neutralize the virus well. The disease progresses through acute, latent, and late stages characterized by declining CD4 counts and opportunistic infections like PCP and Kaposi's sarcoma.

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    5. HUMAN IMMUNODEFICIENCY VIRUS

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    HIV/AIDS was first recognized in 1981 in the US. HIV targets and destroys CD4 T cells, weakening the immune system and allowing opportunistic infections. There are two types, HIV-1 being more prevalent. It is transmitted through sexual contact, blood/blood products, and from mother to child. The virus enters cells through binding proteins on its envelope to CD4 and chemokine receptors on the target cell. It replicates by integrating into the host cell DNA. Antibodies are produced but do not neutralize the virus well. The disease progresses through acute, latent, and late stages characterized by declining CD4 counts and opportunistic infections like PCP and Kaposi's sarcoma.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    32 views24 pages

    Human Immunodeficiency Virus

    Uploaded by

    Malueth Angui
    HIV/AIDS was first recognized in 1981 in the US. HIV targets and destroys CD4 T cells, weakening the immune system and allowing opportunistic infections. There are two types, HIV-1 being more prevalent. It is transmitted through sexual contact, blood/blood products, and from mother to child. The virus enters cells through binding proteins on its envelope to CD4 and chemokine receptors on the target cell. It replicates by integrating into the host cell DNA. Antibodies are produced but do not neutralize the virus well. The disease progresses through acute, latent, and late stages characterized by declining CD4 counts and opportunistic infections like PCP and Kaposi's sarcoma.

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    © All Rights Reserved
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    Download as pptx, pdf, or txt
    of 24

    HUMAN

    IMMUNODEFICIENCY
    VIRUS/AIDS
    BY STEPHEN AYOTI MOKUA.
    DIR.ACCOMODATION AND CATERING
    BRIEF HISTORY

    • AIDS was 1st recognized in US in the summer of 1981, when US CDC reported the
    unexplained occurrence of p.carinii pneumonia in 5 prev healthy homosexual men
    in LA & KC in 26 prev healthy homosexual men in NY & LA.
    • Within mnths it became recognized in male & female iv drug users & soon
    recipients of blood transfusion & hemophiliacs.
    • In 83, HIV was isolated from pt wth lymphadenopathy & in 84 it was demonstrated
    to be the causative agent for AIDS.
    • In 85 ELISA was developed which led to appreciation of scope & evolution of HIV
    epidermic at 1st in US & other developed nations & ultimately throughout the world.
    MORE ABOUT HIV
    (ETIOLOGIC AGENT)
    • HIV belongs to the family of retroviruses & subfamily of lentiviruses
    • There are 2 types i.e HIV-1 & HIV-2.
    • Most common cause of HIV disease throughout the world is HIV-1.
    • HIV-2 was 1st identified in West Africa in 86 & was originally confined to that
    region.
    • HIV preferentially infects and kills (CD4) T lymphocytes resulting in loss of
    cell-mediated immunity & a high probability that host will develop opportunistic
    infections.
    MORPHOLOGY
    • HIV virion is an icosahedral structure containing numerous ext. spikes
    formed by 2 major envelope proteins, ext gp 120 & transmembrane gp 41
    • The virion buds from the surface of infected cell & incorporates a variety
    of host proteins including MHC class 1 & 11 antigens in its lipid bilayer.
    Cont…
    • HIV genome is the most complex of known retroviruses.
    • In addition to the 3 typical retroviral genes gag, pol, & env, which encode
    structural proteins, the genome RNA has 6 regulatory proteins.
    • 2 of the regulatory genes tat & rev are required for replication & the other 4
    nef, vif, vpr, & vpu are termed accessory genes.
    • Gag gene encodes internal “core” proteins the mst important of which is p24,
    an antigen used in serological tests. Pol gene encodes reverse transcriptase
    which synthesize DNA by using the genome RNA as template, an integrase
    that integrates the viral DNA into cellular DNA, & a protease that cleaves
    various viral precursor proteins.
    • The env gene encodes gp160, a precursor glycoprotein that is cleaved to form
    2 envelope(surface) glycoproteins, gp120 & gp41.
    Cont…
    • 3 enzymes are located within the nucleocapsid i.e reverse transcriptase,
    integrase and protease
    • Reverse transcriptase is the RNA dependent DNA polymerase that is the
    source of family name retrovirus. This enzyme transcribes the RNA
    genome into proviral DNA.
    • Integrase mediates integration of proviral DNA into host cell DNA.
    • Protease cleaves the precursor polyprotein into functional viral
    polypeptides.
    • Regulatory gene tat(trans activation of transcription) gene encodes a
    protein that enhances viral & cellular gene transcription.
    • Tat gene & HIV-encoded regulatory protein called Nef repress synthesis
    of class I MHC proteins, thereby reducing ability of cytotoxic T cells to
    kill HIV infected cells.
    • Rev gene controls the passage of late mRNA from the nucleas into
    cytoplasm.
    • Accessory protein vif(viral infectivity) enhances HIV infectivity by
    inhibiting action of APOBEGC3G, an ezyme that causes hypermutation in
    retroviral DNA.
    HIV antigens
    • Gp 120 and gp 41 are the type specific envelope glycoproteins. Gp 120
    protrudes from the surface & interacts with CD4 receptor(& a 2nd protein,
    a chemokine receptor) on the surface of the cell.
    • Gp 41 is embedded in the envelope & mediates fusion of viral envelope
    with the cell membrane at the time of infection.
    • Group specific antigen, p24 is located in core & is not known to vary.
    Antibodies against p24 do not neutralize HIV infectivity bt serve as
    important serologic markers of infection.
    Summary of the replication cycle
    • Follows the typical retroviral cycle.
    • Initial step of entry in to cell is binding of virion gp120 envelope protein to
    CD4 protein on cell surface.
    • Next virion gp41 mediates fusion of viral envelope with cell membrane &
    viron enters cell.
    • Chemokine receptors such as CXRCR4 & CCR5 proteins are required for
    entry of HIV into CD4 +ve cells.
    • Mutations in gene encoding CCR5 endow individual with protection from
    infection with HIV.
    • People who are homozygotes are resistant to infections & heterozygotes
    progress to disease slowly.
    • After uncoating, the virion RNA dependent DNA polymerase transcribes
    the genome RNA into double-stranded DNA, which integrates into host
    cell DNA & multiple copies of viral DNA can integrate.
    • Integration is mediated by a virus-encoded endonuclease(integrase).
    • Viral mRNA is transcribed from proviral DNA by host cell RNA
    polymerase & translated into several large polyproteins.
    • Gag and pol polyproteins are cleaved by viral encoded protease whereas
    Env polyproteins is cleaved by cellular protease.
    Gag is cleaved to form the main core protein (p24), the matrix protein (p17)
    & several cellular proteins.
    Pol polyproteins is cleaved to form the reverse transcriptase, integrase &
    protease. Cleavage process results in mature infectious virion.
    TRANSMISSION
    sexual transmission

    • Predominant way of transmission.


    • In US app. ~42% of new HIV infections are among homosexuals(men) &
    ~33% new infections from heterosexuals.
    • HIV has been demonstrated in seminal fluid both within infected mononuclear
    cells and cell free states.
    • Virus appears to concentrate in seminal fluid particularly in situations where
    there is increased no. of lymphocytes & monocytes in fluid as in genital
    inflammatory states eg urethritis and epididymitis.
    Transmission by blood and blood
    products
    • Blood transfusion
    • Transplanted tissue
    • Iv drug use.

    • Occupational transmission: healthcare workers and lab workers-sharp


    objects.
    • Maternal –fetal/infant transmission-during pregnancy, delivery or
    breastfeeding.
    Pathogenesis and immunity
    • HIV infects helper T cells & kills them resulting in suppression of cell mediated
    immunity.
    • This predisposes host to various opportunistic infections & certain cancers eg kc
    & lymphoma.
    • Initial infection of genital tract occurs in dendritic cells that line the
    mucosa(langerhan cells), after which local CD4 +ve helper T cells become
    infected.
    • HIV is 1st found in blood 4-11 days after infection.
    • NB: The main immune response to HIV infection consist of cytotoxic CD8 +ve
    lymphocytes. These cells respond to initial infection and control it for many yrs.
    It is the ultimate failure of these cytotoxic T cells that results in the clinical
    picture of AIDS.
    • Cytotoxic T cells loose their effectiveness because so many CD4 helper
    cells have died, thus the supply of lymphokines such as IL-2, required to
    activate cytotoxic T cells is no longer sufficient.
    • antibodies against various HIV proteins such as p24, gp120 & gp41 are
    produced bt they neutralize virus poorly in vivo & appear to have little
    effect on course of disease.
    • HIV has 3 main mechanisms by which it evades immune system.
    • 1) integration of viral DNA into host cell DNA, resulting in persistent
    infection
    • 2) high rate of mutation of env gene
    • 3) production of tat & nef proteins that down regulate class I MHC
    proteins required for cytotoxic T cells to recognize & kill HIV infected
    cells.
    Clinical findings.
    • 3 stages
    • 1) Early, acute stage
    • 2) Middle, latent stage
    • 3) Late immunodeficiency state

    • Acute stage begins 2-4 wks after infection, a mononucleosis like picture of fever, lethargy, sore throat
    & generalized lymphadenopathy occurs.
    • A maculopapular rash on trunk, arms & legs (bt sparing palms & soles) is seen.
    • Leukopenia occurs bt no CD 4 cells is usually normal
    • A high level of viremia typically occurs & the infection is readily transmissible during this acute stage.
    • Resolves in abt 2 wks. Resolution is accompanied by lower level of viremia & a rise in no of CD 8
    +VE (cytotoxic) T cells directed aganist HIV
    • After initial viremia, viral set point occurs which can differ from one
    person to another.
    • Set point represents the amount of virus produced i.e viral load & tends to
    remain “set” or constant for yrs.
    • Viral load is important for mngt of pt.
    • CD4 +ve T cells is another important measure that guides in mngt of pt.
    • Used to determine whether the pt needs chemoprophylasis against
    opportunistic org, to determine whether pt needs anti-HIV therapy &
    determine response to this therapy.
    Middle stage
    • In untreated pt, latent stage lasts 7-11 yrs.
    • Pt is asymptomatic during this period.
    • A large amount of HIV is being produced by lymph node cells bt remain
    sequestered within lymph nodes.
    • A syndrome called AIDS related complex(ARC) can occur in latent stage.
    • Manifests wth persistent fever, fatigue, wt loss, & lymphadenopathy.
    Late stage/AIDS
    • Decline in no of CD4 cells below 400/micro L. & increase in frequency & severity of opportunistic
    infections.
    • 2 most characteristic manifestations of AIDS are pneumocystis pneumonia & KC.
    • other opportunistic infections include
    disseminated herpes simplex
    1. Herpes zoster
    2. Cytomegalovirus
    3. Progressive multifocal leukoencephalopathy
    4. Thrush(candida albicans)
    5. Cryptococcal meningitis
    6. Disseminated histoplasmosis
    7. Toxoplasmosis
    8. Cryptosporidiosis
    9. TB

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