Case Study: Human Immunodeficiency Virus – Flashcards
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What is the causative agent of AIDS?
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HIV - Human immunodeficiency virus
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What type of virus is HIV?
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Retrovirus
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What is the diameter of HIV?
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100-120nm
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What is the genetic material of HIV?
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2 single strands of positive sense RNA
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Does HIV have a lipid envelope?
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Yes
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What are the main proteins of HIV? (6)
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p24 gp120 gp41 reverse transcriptase integrase protease
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What are the two most common ways HIV enters the body?
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Mucosal surface Injected by contaminated needles
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What is the main way HIV is transmitted?
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Via sexual intercourse
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Why is HIV particularly infectious?
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It is relatively labile
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What are the target cells of HIV in the body?
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Th cells
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What molecule on the surface of Th cells does gp120 on HIV bind to?
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CD4
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What molecule on HIV binds to the CD4 of Th cells?
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gp120
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What mechanism does HIV use to enter a host cell?
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Fusion
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What does interaction of the virus with CCR5 cause? ...What does this allow?
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Irreversible conformational changes in envelope glycoproteins allowing fusion of the viral envelope with the cell membrane
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Why are memory CD4+ T cells the primary target of HIV?
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They have a high expression of CCR5
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Why can dendritic cells also be infected by HIV?
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They are CD4+ and a surface HIV receptor
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What do the dendritic cells do when hey become infected with HIV?
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Migrate to local lymph nodes and present processed peptides to Th cells - virus comes into contact with CD4 and CCR5 and infects
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Where does HIV migrate to following initial infection?
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Lymph nodes Primary lymphoid organs Mucosal surfaces (especially GALT)
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What is viraemia?
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Virus in the blood
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What does infection of large number of Th cells lead to?
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Viraemia
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What are the 3 phases of infection of HIV?
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Acute Chronic AIDS
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What events occur in the acute phase of infection with HIV? (6)
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-Production of virus by Th cells leads to detectable viraemia at 7-14 days after infection -Increase in Tc cells to HIV infected cells -Antibodies evolve to become against gp41 and gp120 -Levels of circulating Th cells decreases -Latently infected Th cells and DC cells harbouring the virus remain -Level of viraemia settles to set point
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When does the production of viruses by Th cells lead to detectable viraemia?
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7-14 days after infection
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What does a higher level of viraemia lead to? (2)
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Increased infection of other areas of the body Increased transmission
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By how much does the action of Tc cells specific to HIV infected cells reduce the viral load? ...Over how long?
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10-100 fold 2-6 months
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What antibodies to HIV originally specific to?
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p24
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What do p24 specific Anti-HIV evolve to become specific to? (2)
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gp41 gp120
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What antibodies persist at high levels throughout life? (2)
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Anti-gp41 Anti-gp120
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When do neutralising antibodies appear?
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Once viraemia has greatly decreased
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What happens in the chronic pause of infection of HIV? (2)
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Th cells gradually decrease further Viraemia gradually increases
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What is the set point?
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A point of equilibrium that the viral load settles to after the acute phase of infection
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What does the set point represent?
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The balance between production of new virions and control by the immune system
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What is the clinical latency period?
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The period of infection where there are no symptoms
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At what CD4 count is a patient considered to be in the AIDS phase of HIV infection?
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200 cell/mm^3 (or less)
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What does AIDS stand for?
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Acquired Immunodeficiency Syndrome
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What is the range of times that a patient can take to progress into full-blown AIDS?
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Few months - 10 years
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What are patients that take a long time to progress into full-blown AIDS termed as?
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Long-term nonprogressors
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What is the key event that leads to the immunodeficiency associated with AIDS?
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Death of CD4+ T cells
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What are the main mechanisms of Th cell death in AIDS? (2)
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-Direct death of infected Th cell as the result of a massive infection -Apoptosis of Th cell mediated by Tc recognising that the cell is infected
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Why does the depletion of Th cell from the body lead to such immunodeficiency?
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Together with DCs, it control the development and function of most immunological cell types
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How can infected dendritic cells cause some of the immunodeficiency associated with AIDS?
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These cells affect the early differentiation of Th0 cells to Th1 and Th2 Disruption of this disrupts all immune responses
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What are the main changes that occur in primary lymphoid tissues the contribute to the immunodeficiency associated with AIDS? (4)
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-Infection of thymocytes leading to decreased output of CD4+ T cells -Changes to thymus stromal cell function -Loss of tissue architecture in the thymus -Bone marrow depression
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What are the main changes that occur in secondary lymphoid tissues the contribute to the immunodeficiency associated with AIDS?
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Polyclonal activation of Tc cells and B cells Reduction in activation of Th cells
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When do symptoms of HIV infection first occur?
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Around 2-8 weeks after exposure
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What are the common clinical symptoms presented with an HIV infection?
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(Infectious mononucleosis like illness) -Fever -Maculopapular rash -Sore throat -Night sweats -Malaise -Lymphadenopathy -Diarrhoea -Mouth ulcers -Genital ulcers
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What clinical symptom do one third of patients in clinical latency develop following the acute infection phase?
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Persistent generalised lymphadenopathy
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What happens to viral load and CD4+ count as the infection progresses into AIDS?
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Increases Decreases
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What may a patient present when their CD4+ count falls below 200 cells/mm^3?
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An AIDS defining illness
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What may a patient present when their CD4+ count falls below 200 x10^6 cells/mm^3?
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Opportunistic infections
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What types of infections are included in the opportunistic infections associated with AIDS?
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Bacterial Viral Fungal Cancers
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What are HIV positive patients most likely to die from?
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Opportunistic infections (rather than HIV directly)
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What is the most common neoplasm associated with HIV infected individuals?
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Kaposi's sarcoma
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What are the common sites of Kaposi's sarcoma tumours? (2)
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Skin Gums of the mouth
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What causes Kaposi's sarcoma in HIV infected patients?
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HHV-8 (aka KSHV)
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What is the diagnosis of HIV based on?
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Detecting specific antibodies, antigens, or both
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What are some of the common techniques used for diagnosing HIV?
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Western blotting Anti-HIV assays ELISA Real time PCR
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What is real time PCR used for?
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Detecting viral RNA
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Why are tests to diagnose HIV to antibodies and antigens?
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Antibody is not present in the earliest stage of infection
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What test has to be used in order to detect HIV infection in a newborn? ...Why?
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Tests to detect viral nucleic acids and proviral DNA Because mothers IgG to HIV can persist in the newborn for up to 15 months
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Why are levels of CD4+ T cells and viral load measured?
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To determine what stage of the disease the patient is in
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What does viral load determine?
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The rate of destruction of the immune system
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What does the level of CD4+ cells indicate? (2)
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The degree of immunodeficiency and likelihood of developing opportunistic infections
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What is the aim of HIV therapies?
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To reduce the replication of a persistently expressed chronic virus infection to a non-detectable level
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Why do HIC therapies not lead to the eradication of the virus from the body?
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Some HIV genomic information has been integrated into host cells
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What are the main types of antiretroviral drugs currently in use?
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Reverse transcriptase inhibitors Protease inhibitors Fusion inhibitors CCR5 inhibitors HIV integrase inhibitors
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What are the two classes of reverse transcriptase inhibitors?
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NRTIs - Nucleoside NNRTIs - Non nucleoside
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What contributes to the massive diversity in HIV viruses? (3)
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High rate of mutation Ability to recombine RNA polymerase has no proof reading
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What does HAART stand for?
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Highly active antiretroviral treatment
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What different types of topics should be targeted for intervention to inhibit the spread of HIV?
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Sexual health Drug abuse Blood plasma products Antenatal screening
