Human Immunodeficiency Viruses 2024 PDF

Human Immunodeficiency Viruses Dr. Mohamed El-Sweify Professor of Microbiology & Immunology 2024 Objectives: By end of this lecture, students will be able to: 1- Illustrate Structure and Morphology of HIV 2- Explain different Targets of HIV in human body 3- E...

Human Immunodeficiency Viruses Dr. Mohamed El-Sweify Professor of Microbiology & Immunology 2024 Objectives: By end of this lecture, students will be able to: 1- Illustrate Structure and Morphology of HIV 2- Explain different Targets of HIV in human body 3- Explain Virus replication cycle for HIV 4- Mention the Clinical picture of AIDS 5- Describe the Lab diagnosis of HIV 6- Explain the source and transmission of HIV in Human 7- Detail the Precaution to avoid HIV transmission  2- Structure and Morphology of HIV HIV-1 and HIV-2 viruses belong to “Retrovirus Family” HIV is an Enveloped virus, contains 2 copies of +sRNA and Reverse transcriptase (RT), protease and integrase enzymes. Viral RNA carries 3 main sets of genes: Gag gene: which code for group-specific antigen, capsid, matrix, and nucleic acid-binding proteins Pol gene: which code for polymerase, protease, integrase enzymes Env gene: which code for envelop glycoproteins: gp160 and gp41 Important protein markers of HIV ‫هام جدا‬  3- What are the target cells for HIV ? These are the cells which carries the proper receptors, to which the viral gp120 binds and allows entry of HIV to these cells; they are: 1) CD4 molecule is the main receptor 2) Other co-receptor are: 1. Chemokine receptor CCR5 on myeloid cells mainly, and also on T- helper subsets (for macrophage-tropic R5 HIV strains) 2. CXCR4 receptor mainly on T4 helper cells. (for the T cell-tropic X4 strains). 3. DC-SIGN: on dendritic cells 4. Α4, β7 integrin receptor on gut-associated lymphoid tissue (GALT) Hence, T4+ lymphocytes and Macrophages are the main targets for HIV infection and replication. This leads to depression of immune responses (mainly the cell- mediated). Persons with (homozygotic) missing CCR5 are highly resistant to HIV infection.  4- Viral Replication Cycle: see next fig 1. Attachment to virus receptors on host cell, and subsequent Fusion of virus envelop with host cell membrane 2. Entry of RNA, reverse transcriptase, integrase, into cell 3. Intermediate viral DNA is transcribed in cytoplasm by RT 4. This DNA cross nuclear membrane and integrates into nucleus by viral integrase. 5. New viral genomic +sRNA is formed, which acts as mRNA and start to form viral proteins for the new virus 6. New viral RNA and new viral proteins move to cell surface membrane to become new immature virus, that buds throhgh the membrane (cell membrane forms and envelop for HIV) 7. After budding, the protease enzymes split the viral polyprotein into functional proteins, which are: ……….. Now the virus becomes mature virion, able to infect another cell.  5- Clinical Picture: I.P. : up to 7-10 years. Diseases: 3 categories A) Asymptomatic, with persistent generalized lymphadenopathy B) Weakened CMI, or C) Defined AIDS: Opportunistic viral, bacterial, fungal, and protozoal infections and Malignomas. D) Cause of Death: uncontrolled opportunistic infections Prophylaxis: No specific vaccination ….yet !! ‫هام جدا‬ ‫جدا‬  Symptomatic diseases due to HIV infection (i.e. AIDS picture) I. Opportunistic infections 1) Protozoal infections: toxoplasma of brain Cryptosporidiosis with diarrhea Isosporiasis with diarrhea 2) Bacterial infections: Mycobacterium avium-intracellulare (disseminated) Any Atypical mycobacteria Extrapulmonary tuberculosis Salmonella septicemia Pyogenic infection 3) Fungal infections: Candidiasis of oesophagus, trachea, lungs Cryptococcus neoformans (lungs→ brain) Pneumocystis carinii (lungs→ brain) Histoplasmosis (disseminated) Coccidiomycosis (disseminated)  Clinical diseases due to HIV infection (i.e. AIDS picture)…… 4) Viral infections: Cytomegalovirus Herpes virus (H. simplex) Epstein-Barr virus Recurrent Respiratory viruses II. Opportunistic neoplasias: Kaposi sarcoma, primary lymphoma of brain, and non-Hodgkin lymphoma. III. Others: HIV wasting syndrome, and HIV encephalopathy.  6- Lab Diagnosis of HIV (see graph in slide # 10) 1- Detection of viral RNA in blood: by RT-Real Time PCR (quantitative for viral load), during acute recent infection or late stage disease (after AIDS symptoms)...and to follow up after treatment. 2- Detection of viral antigens in blood: p24 Ag during acute recent infection before Abs appear; or late stage disease (after AIDS symptoms occur). 3- Detection of antibodies in blood to viral antigens: At least Positive Abs to p24; and gp41/gp160 are diagnostic for HIV-1 infection… - Other Abs to p31, p18, gp120, p 55 are also included in EIA and the confirmatory Western blot assays. 4- Viral culture is not done. Western-blot result for HIV-1 diagnostic assay 7- Where the virus could be found in human secretions..? HIV is found in varying concentrations or amounts in: Blood Semen May Transmit Vaginal secretion HIV Infection Breast milk Saliva Unlikely to Tears. Transmit HIV Infection  HIV is transmitted by: 1. Sexual contact with an infected person 2. Sharing needles and/or syringes. 3. Blood transfusions of infected blood or blood clotting factors. 4. Babies born to HIV-infected women may become infected before or during birth or through breast- feeding after birth.  HIV in the Environment HIV does not survive well in the environment, making the possibility of environmental transmission remote. Household Transmission HIV is rarely transmitted between family members. Cases resulted only from contact between skin or mucous membranes and infected blood from patient.  What about Saliva, Tears, and Sweat ? In saliva and tears, HIV is present but in very low quantities in some AIDS patients. So, Contact with saliva, tears has never been shown to result in transmission of HIV ❑ It is important to understand that finding a small amount of HIV in a body fluid does not necessarily mean that HIV can be transmitted by that body fluid. ❑ HIV has not been recovered from the sweat of HIV-infected persons.  Precautions to prevent infection among housholds and healthcare staff: 1. Gloves should be worn during contact with blood or other body fluids that could possibly contain visible blood, such as urine, feces, sputa, or vomit. 2. Cuts, sores, or breaks on both the care giver’s and patient’s exposed skin should be covered with bandages 3. Hands and other parts of the body should be washed immediately after contact with blood or other body fl. 4. Surfaces soiled with blood should be disinfected. Precautions to prevent infection among housholds and healthcare staff:… 5. All Practices that increase blood contact, such as sharing of razors, shaving brushes and toothbrushes, should be avoided. 6. Instruments that penetrate skin, e.g. tattooing and acupuncture needles, ear piercing, should be used once or cleaned and sterilized.  Tasks: (True or False) 1- HIV contains dsRNA 2- HIV is an enveloped virus 3- HIV contains carbohydrate surface attachment receptors 4- HIV is transmitted by sexual contact 5- HIV is resistant to harsh environmental conditions