متلازمة العوز المناعي المكتسبة Acquired Immunodeficiency syndrome (AIDS) Human Immunodeficiency virus HIV Retroviridae R. Gllo – 1978 Retrovirus – Lymphocytes – Leukemia Yori Hinuma – 1981 HTLV – I

Luc Montagnier – 1983 (HIV-1) HTLV – 3 Human T-Lymphotropic virus – III >40 M infected w/ HIV / AIDS 2002 Oncogen جينات مسرطنة Except – Subfamily – Lentivirinae Virus Envelope / 100nm , ss RNA Structural Genes

Gag gene: Matrix (P18) (MA) Capsid (P24) (CA) Nucleocapsid (P15) (NC)

Pol gene: Protease (p10) (PR) RT (P 51/66) (RT) Integrase (P34) (IN)

Env gene Surface (gp 120) (SU) Transmembrane (gp 41) ( TM ) (tat, art, orf)

HIV – T-Lmphotropic (T-cell) T-Cell / Cell – mediated Response (CTL) Macrophages …. . HIV Cytotoxic-T-Cell Helper–T–Cell B-Cell (CTL) (Ab) Activation Activation

HIV - Biology

Pathogenesis and Pathology HIV course of infection I- Acute infection + Seroconversion II- Chronic infection PGL: Persistent Generalized Lymphadenopathy ARC: AIDS related complex III- AIDS Syndrome Untreated HIV infection / decade

Primary infection + dissemination: 4-11 day / mucosal and viremia Viremia / 8-12 weeks Dissemination to Lymphoid Organs Macrophages and monocytes Acute monoucleosis – like Syndrome CD4 T-Cell numbers drops Immune response / 1week- 3months HIV persist in Lymph nodes

Clinical Latency + HIV expression: Last For 10 Years High Level of Viral – replication Virus Life-Cycle (2.6 days) CD4 + T-Lymphocytes / Viral – Replication CD4 + Cell Life-cycle (1.6 days)

Clinical disease + death: Primary infection and clinical disease/ 10 years Untreated Cases / 2 years / death Constitutional symptoms such as opportunistic infection/ or neoplasms High- Level of Virus/ more Virulent M- tropic to T-tropic / AIDS progression

Clinical Finding / Acute HIV infection Non – Specific: Fatigue, Rash, Headache, Nausea and Night Sweats. AIDS: Suppression of the Immune system Opportunistic infections or neoplasms (Kaposi’s sarcoma) Neurological disease (encephalitis, aseptic meningitis)

المناعة Immunity Immune Responses / HIV Ag’s Ab’s to envelope (gp41,120,160) maintained Ab’s to core (gp24) decline/ clinical signs

Diagnosis Virus isolation: HIV – Cultured in peripheral Blood Serology: ELISA – HIV antibodies NA and Antigens: RT – PCR + bDNA assay

طرق انتقال الفيروس Transmission: Sexual intercourse Blood + B. Products Contaminated needles Organ transplant Mother to child Other methods

Prevention, Treatment and Control Antiviral Drugs: RT- inhibitors: (AZT, 3TC and Nevirapine ,delavirdine) PR inhibitors: Indinavir, Ritonavir HAART: Highly active antiretroviral therapy

Vaccine: HIV mutate rapidly Not expressed in all infected Not Completely cleared From immune respons after primary infection Lack of animal model for HIV