HIV - Retroviruses PDF

Retroviridae  RETROVIRIDAE Genome: ss (+) RNA genome (2 identical copies) Icosahedral capsid (conical capsid for HIV) Enveloped viruses, 80-120 nm They encode an DNApol – RNAdep (reverse transcriptase) and replicate through a DNA intermediate. The DNA...

Retroviridae  RETROVIRIDAE Genome: ss (+) RNA genome (2 identical copies) Icosahedral capsid (conical capsid for HIV) Enveloped viruses, 80-120 nm They encode an DNApol – RNAdep (reverse transcriptase) and replicate through a DNA intermediate. The DNA copy of the viral genome is integrated into the host chromosome to become a cellular gene. Human Immunodeficiency Virus (HIV) Acquired Immunodeficiency Syndrome (AIDS) is one of the most clinically relevant endemic diseases, caused by two lentiviruses HIV-1 and 2.  Human Immunodeficiency Virus (HIV-1) o Gag: (group-specific antigen) core and capsid proteins o Pol: (polymerase) reverse transcriptase, protease, integrase o Env: (envelope) glycoproteins o Pro: protease o Tat: transactivation of viral and cellular genes Virulence-enhancing proteins o Rev: regulation of RNA splicing and promotion of export to cytoplasm HIV – VIRAL REPLICATION CYCLE  HIV – RECEPTOR AND CO-RECEPTORS CCR5 (macrophages) CD4+ CXCR4 (T-cells) Specific cell receptor for HIV= CD4 The chemokine receptors CXCR4 and CCR5 function as coreceptors for HIV-1 entry into CD4+ cells. They HIV-1 primarily infects CD4-expressing T cells are needed to activate the fusion of membranes and and cells of the myeloid lineage (monocytes, HIV entry into the target cell. During the early stages of macrophages, alveolar macrophages of the lung, HIV infection, viral isolates tend to use CCR5 for viral dendritic cells, and microglial cells of the brain). entry, while later isolates tend to use CXCR4. HIV – INTEGRATION HIV - TRASMISSION HIV is transmitted by blood, semen and vaginal secretions HIV is vertically transmitted: transplacental, perinatal, breast feeding HIV DISEASE PROGRESSION ACUTE INFECTION Primary infection of cells in blood or mucosa (HIV directly infects CD4+ T cells, macrophages and dendritic cells) Viral replication in the regional lymph nodes leads to exponential viral growth and widespread dissemination Development of anti-viral responses and symptoms of acute infection occur Decrease in plasma viral load and symptoms of acute infection resolve  HIV DISEASE PROGRESSION CLINICAL LATENCY o During this period of the disease, the immune systems remains competent at handling most infections with opportunistic microbes. o Few or no clinical manifestations. o Steady destruction of CD4+ T cells in lymphoid organs and steady decline of circulating blood CD4+ T cells  HIV DISEASE PROGRESSION AIDS Acquired Immune Deficiency Syndrome o CD4+ cell count less than or equal to 200 per microliter o Catastrophic breakdown of host defenses, marked increase in viremia and clinical disease. o Clinical Features: o Opportunistic infection o Neoplasia o CNS involvement HIV causes lytic and latent infection of macrophage, dendritic cells, and CD4 T cells and disrupts neuron function. The outcomes of these actions are immunodeficiency and AIDS- dementia  HIV - PATHOGENESIS 1. Acute HIV infection o Non-specific symptoms (flu or mononucleosis-like symptoms, lymphadenopathy, diarrhea) o High viral load - up to 10 million copies/ml blood (highly infectious) o Collapse of CD4+ T cells o It lasts about 2-3 months  HIV - PATHOGENESIS 2. Host’s immune response o Drop of viremia o Host immune response (specific antibodies appear) o The immune response is NEVER sterilizing  HIV - PATHOGENESIS 3. Clinical latency o Asymptomatic phase o Infection is constantly active o Virus persists in dendritic cells and macrophages in the lymph nodes o Virus persists as a pro-virus in quiescent lymphocytes o Slow and steady decline of CD4 + T cells o It lasts several years (2-15)  HIV - PATHOGENESIS 4. Initial phase of the disease o Massive loss of CD4+ T cells: proliferating lymphocytes are killed by the virus o Mutation of the viral strain allows evasion from the host's immune response  HIV - PATHOGENESIS 5. Advanced phase - AIDS o CD4+ count