HIV- AIDS BY DR BASHIR AHMED DAR ASSOCIATE PROFESSOR MEDICINE CHINKI PORA SOPORE KASHMIR EMAIL—firstname.lastname@example.org
AIDS is caused by human immunodeficiency virus • Genetically the virus has two types • HIV-1 (World wide) • HIV-2 which is less aggressive slow and restricted mainly to western Africa.
How it got transferred to humans • The HIV-1 actually got transfered from African green monkeys
How it got transferred to humans • HIV-2 got transferred from Sooty managbey monkeys or Chimpanzees
Natural transfer theory • Commonly held theory is that HIV got transferred through hunting and handling of chimpanzees and through slaughtering and eating “bush meat” of these (monkeys).The epidemic required urbanization and increased population mobility
Human error theory • Oral polio vaccine or some other injectable vaccines used enmass in West Africa during the late 1950s may have been contaminated with HIV since these vaccines were prepared by using these monkeys or their tissues in process of their preparation.
How HIV can be transmitted • Unprotected sexual contact – be it vaginal, oral, or anal Mucosa - with an infected partner • Contact of abraded skin or mucosa with body secretions such as blood, CSF or semen;
How HIV can be transmitted • Sharing unsterilized needles or syringes with an HIV positive person, for example, when using drugs or in a healthcare setting. • During pregnancy or birth and through breastfeeding from an HIV positive mother to her baby. • Blood transfusions with infected blood • Accidental occupational exposure
Populations particularly at risk • Has a sexually transmitted infections(STIs) • Has anal sex with her/his partner(s) • Exchanges sex for money or drugs • Has many sex partners • Non-circumcised
Populations particularly at risk • Leads life separated from spouse due to professional obligations (e.g., truck drivers, laborers, migrants) • Homosexuals/ bisexuals • Certain sexual practices increases the disease • Like sexual Contact with • Male-to-male • Female-to-female
How HIV can NOT be transmitted • Through air or by coughing and sneezing • Through food or water • Through sweat and tears
How HIV can NOT be transmitted • By sharing cups, plates, and utensils with an infected person • By touching, hugging and kissing an infected person • By sharing clothes or shaking hands with an infected person • By sharing toilets and bathrooms with an infected person • By living with an infected person • By mosquitoes, fleas, or other insects
How HIV can NOT be transmitted • While the virus has occasionally been found in saliva, tears, urine and bronchial secretions, transmission after contact with these secretions has not been reported. • No laboratory or epidemiological evidence suggests that biting insects have transmitted HIV infection.
CONCENTRATION OF VIRUS • Blood, Menstrual Blood – Very High • Vaginal Fluids, Semen, Pre ejaculate Fluid – High • Bone Marrow – High • Saliva – No • Sweat, Tears, urine - No
HIV in Body Fluids Blood 18,000 Semen 11,000 Vaginal Fluid 7,000 Amniotic Fluid 4,000 Saliva 1 Average number of HIV particles in 1 ml of these body fluids
HIV STRUCTURE • HIV belongs to a special class of viruses called retroviruses. Within this class, HIV is placed in the subgroup of lentiviruses. • Other lentiviruses include SIV, FIV, Visna and CAEV, which cause diseases in monkeys, cats, sheep and goats. • All viruses except retroviruses contain DNA
HIV STRUCTURE • So Retroviruses are the exception because their genes are composed of RNA (Ribonucleic Acid). • However RNA has a very similar structure to DNA with small differences
HIV STRUCTURE • HIV has just nine genes (compared to more than 500 genes in a bacterium • Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles.
HIV STRUCTURE • The other six genes, known as tat, rev, nef, vif, vpr and vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease.
HIV STRUCTURE • An HIV particle is around 100-150 billionths of a metre in diameter. That's about the same as: • 0.1 microns • 4 millionths of an inch • one twentieth of the length of an E. coli bacterium • one seventieth of the diameter of a human CD4+ white blood cell.
HIV STRUCTURE • HIV particles surround themselves with a coat of fatty material known as the viral envelope . • This envelope gives out lots of little spikes around 72 in number.
HIV STRUCTURE • These spikes are made of knobs and handles made of proteins gp120 and gp41 respectively.
HIV STRUCTURE • Just below the viral envelope is a layer called the matrix, which is made from the protein p17(Matrix proteins)
HIV STRUCTURE • Below the matrix is another layer of proteins P24 forming viral core (or capsid) and is usually bullet-shaped.
HIV STRUCTURE • Inside the core are three enzymes required for HIV replication called • Reverse transcriptase • Integrase • And protease
HIV STRUCTURE • Also held within the core is HIV's genetic material, which consists of two identical copies of single stranded RNA.
The virus, entering through which ever route, acts primarily on the following cells: • * Lymphoreticular system: • o CD4+ T-Helper cells • o CD4+ Macrophages • o CD4+ Monocytes • o B-lymphocytes • *
The virus, entering through which ever route, acts primarily on the following cells: • Certain endothelial cells • * Central nervous system: • o Microglia of the nervous system • o Astrocytes • o Oligodendrocytes • o Neurones - indirectly by the action of cytokines and the gp-120
Pathogenesis • HIV binds to CD4 molecule, CD4 molecule is found on the T helper-cell Macrophages etc.Binding of CD4 is not sufficient for entry • Therefore gp120 protein also binds to co-receptor • CCR5 Co-receptor - is used by macrophages • CXCR4 Co-receptor - is used by lymphocytes
Pathogenesis • Binding of virus to cell surface results in fusion of viral envelope with cell membrane of T-helper cell and thus Viral core is released into cell cytoplasm • After uniting with T-helper cells the T-Helper cells through • Th1 - activate Tc (CD8) lymphocytes, promoting cell-mediated immunity • Th2 - activate B lymphocytes, promoting antibody mediated immunity
Pathogenesis • CD8 Cytotoxic T lymphocyte (CTL) is Critical for containment of HIV.Derived from T8 cells, recognize viral antigens and directly destroy infected cells
Pathogenesis • Antibodies formed bind to surface of virus to prevent attachment to target cells • Fc portion of antibody also binds to NK cells and Stimulates NK cell to destroy infected cell
Pathogenesis • Numerous organ systems are infected by HIV: • Brain: macrophages and glial cells • Lymph nodes and thymus: lymphocytes and dendritic cells • Blood, semen, vaginal fluids: macrophages • Bone marrow: lymphocytes • Skin: langerhans cells • Colon, duodenum, rectum: chromaffin cells • Lung: alveolar macrophages
Pathogenesis • About (10 billion) virions are produced daily • Average life-span of an HIV virion in plasma is ~6 hours • Average life-span of an HIV-infected CD4 lymphocytes is ~1.6 days • HIV hides in cells like CNS etc and can lie dormant within a cell for many years, especially in resting (memory) CD4 cells, unlike other retroviruses etc
Pathogenesis • All elements of immune system are affected. Advanced stages of HIV are associated with destruction and disruption of lymphoid tissue(T-helper cells etc) that result in • Impaired ability to mount immune response • Impaired ability to maintain memory responses • Loss of containment of HIV replication • ultimately results in severe immunosuppression susceptibility to opportunistic infections
HIV Life Cycle • Step 1: Attachment of virus at the CD4 receptor and chemokine co-receptors CXCR4 or CCR5
HIV Life Cycle • Step 2: viral fusion and uncoating