CONTENTS Introduction of HIV HIV vaccines History & origin Microbicides Crossgenesis & systematic Agents And Factors position Responsible For Causing Structure AIDS other than HIV Antigenic variation & Some myths about AIDS diversity Current researches on HIV genome AIDS Life cycle Working of immune system Pathogenesis & stages of HIV infection Clinical features Epidemiology & transmission Diagnosis
HIVHuman Immunodeficiency VirusSimilar to SV40 & HTLVAn HIV particle is around 100-150 billionths of a meter in diameter.Genetic material is ss-RNAHIV exhibits cell tropism for CD4 receptor cells • The property of particular microorganism to infect a particular cell is called cell tropism.
HISTORYHIV probably transfers to humans in Africa between 1884 and 1924.The name “AIDS” – Acquired Immuno Deficiency Syndrome – is created:1982Montagnier reported causative agent of AIDS & called it LAV:1983Gallo isolated reterovirus & called it HTLV-III :1983Scientists identify HIV (initially called HTLV-III or LAV) as the cause of AIDS: 1984An HIV test is licensed for screening blood supplies :1985AZT is the first drug approved for treating AIDS :1987The Joint United Nations Programme on AIDS (UNAIDS) is established :1995
OriginThe hunter theory• The most commonly accepted theory• SIVcpz was transferred to humans as a result of chimps being killed and eaten or their blood getting into cuts or wounds on the hunter.The oral polio vaccine (OPV) theory• live polio vaccine needs to be cultivated in living tissue, and initially it was grown in kidney cells taken from local chimps infected with SIVcpz.
The hepatitis B theory• chimpanzees, contaminated with numerous viruses, were used to produce hundreds of hepatitis B vaccine doses administered to central African Blacks along with homosexual men.The conspiracy theory• A survey carried out in the US, identified a significant number of African Americans who believe HIV was manufactured as part of a biological warfare program, designed to wipe out large numbers of black and homosexual people.• Most contradicted theory as thought to be iatrogenic.• Supports for hepatitis B theory
CROSS GENESISHIV-2 corresponds to SIVsm, a strain ofthe Simian Immunodeficiency Virusfound in the sooty mangabey, which isindigenous to western Africa.
FamilyRETEROVIRIDAE SUB FAMILY LENTIVIRINAE Subgroup LENTIVIRUS
Generalized Structure of HIV Viral envelope (lipid membrane) 72 little spikes, which are formed from the proteins gp120 and gp41 Matrix, which is made from the protein p17 Viral core (capsid) is bullet-shaped and is made from the protein p24 Three enzymes reverse transcriptase, integrase and protease Two identical strands of RNA.
Antigenic variation & diversity Highly mutable virus Exhibits frequent antigenic variation as well as differences in other features such as nucleotide sequences, cell tropism & cytopathology Not only are there differences between isolates of HIV from different places or persons but also between sequential isolates from same person & even between those obtained from different site of the same person at the same time This is due to the reverse transcription. These hypermutant forms of HIV are known as "circulating recombinant forms" or CRFs
Antigenic structure HIV has 3 antigen types: Envelope antigen- glycosylated polyproteins & antibodies to these proteins are always present in the serum of HIV infected person. Core antigen- antibodies to these proteins are also present in the serum of HIV infected person. RT antigen (reverse transcriptase)- antibodies are found in the patient of AIDS.
GroupsVirus Types (subtypes) M (A, B, C, D, F, G, H, J, K) O HIV 1 NHIV P HIV 2 No data
Genome of HIVHIV has following genes• Genes coding for structural proteins- • Gag, pol, env• Genes coding for non structural & regulatory proteins- • Vif, vpr, tat, rev, vpu, nef rev gag vif tat tat nef pol vpr vpu env
Genes coding for structural proteins gag- determines the core & shell of the virus P17, P 24, P55 pol- codes for the 3 enzymes found in the core of virus Polymerase reverse transcriptase, integrase, protease env- determines the synthesis of envelope glycoprotein gp160 Gp120, gp41 gag pol env
Vif- viral infectivity factor gene influences the infectivity of viral particles. Vpr- stimulates the promoter region of virus. Tat- trans activating gene which enhances the expression of all viral genes. Rev- regulator of virus gene which enhances the expression of structural proteins. Vpu (HIV1)/ Vpx (HIV2)- enhances the maturation & release of progeny virus from cells. Nef- negative factor gene which downs the replication of virus. rev vif tat tat nef vpr vpu
1. ADSORPTION2. PENETRATION3. REVERSETRANSCRIPTIONLIFE CYCLE OF
4. INTEGRATION5. TRANSCRIPTION6. ASSEMBLY& RELEASE LIFE CYCLE OF
HIV and the Immune SystemWhen infection occurs through a mucosal surface, the virus is taken up bysubmucosal Langerhans cells, which transport it to the regional lymph nodes,where it is transmitted to CD4+ T cellsWhen the virus is introduced directly into the blood stream, it will most likelybe filtered in the spleen, adsorbed by Monocytes, macrophages, and relatedcells, which express CD4-like moleculesThe preferential infection of macrophages and related cells vs. CD4lymphocytes depends on the affinity of HIV strains for co-receptors. Theinfection of macrophages involves interaction with chemokine receptors(CCR-5 or CKR-5) while the infection of CD4+ T cells involves the CXCR-4molecule.
The infection of monocytes, macrophages, andrelated cells is productive but not cytotoxic, andthe infected cells become a source of persistentviral infection.In Humoral immune response, neutralizingantibodies, which inhibit the infectivity of freeHIV in vitro, directed against epitopes of gp120and gp41. ADCC-promoting antibodies, are alsopotentially protective, which react with gp160.
On the negative side, enhancing antibodies, whichreact with gp41 antibodies and enhance HIVinfectivity by an unknown mechanism, have alsobeen demonstrated.Cell-mediated immune responses involve MHC-Irestricted CD8+ T lymphocytes, which recognize avariety of epitopes in gag, env, nef, and pol HIVproteins. Thus, cell-mediated immunity seems ableeither to block infection or to reduce viral replicationto levels tolerated by the immune system.
Monocytes, macrophages, dendritic cells Functional changes in these cells, also some destruction of TH cells, Immunosuppressive viral molecules CD4 receptors TH CEL Depressed immune response initially to L HIV later to unrelated microbial antigensPoor CMI responses neutralizingantibodies produced plus weak T cellresponse Failure to eliminate infection Loss of control of latently carried microbesVirus persists immune defect slowlyincreases, virus load increases, Disease ARC/AIDSpatients remains infectious for life
Stages of HIV infection4 stages of HIV infectionPrimary: No symptoms at allAsymptomatic :• Lasts for an average of ten years• This stage is free from symptomsSymptomatic• The symptoms are mild• Emergence of opportunistic infections and cancersAIDS• The illnesses become more severe leading to an AIDS diagnosis• Secondary or combined immunodeficiency syndrome
Clinical Features of HIV InfectionThe natural course of HIV infection is as follows: 1. Seroconversion illness 2. Incubation period 3. AIDS-related complex or persistent generalized lymphadenopathy, and
4. AIDS• Opportunistic Infections• Opportunistic Tumors• Neurological manifestations• Dermatological Manifestations• Gastrointestinal Manifestations• Manifestations in children and during pregnancy
Opportunistic Infections Protozoal Bacterial Pneumocystis carinii Mycobacterium avium (now thought to be a fungi) complex toxoplasmosis of the brain Extrapulmonary TB crytosporidosis with Salmonella septicaemia diarrhoea multiple or recurrent pyogenic bacterial infection Fungal Viral candidiasis (oesophagus, CMV trachea, lungs) HSV crytococcosis, extrapulmonary VZV histoplasmosis coccidiodomycosis
Opportunistic Tumors Burkitts lymphoma Burkitts-like lymphoma Diffuse large B-cell lymphoma (DLBCL) Primary central nervous system lymphoma Tumours in kaposi’s sarcoma Kaposi’s sarcoma (very common amongst HIV patients) Hodgkins disease Anal and rectal carcinomas Hepatocellular carcinomas Head, neck and lung cancer etc. Enlarged & lobulated tonsils
Immunological abnormalitiesFeatures that Other featurescharacterizes AIDS• Lymphopenia • Decreased in vitro lymphocyte proliferative• Selective T cell response to antigens deficiency (T4:T8 • Decreased cytotoxic ratio inversion) response by T cells & NK• Decreased delayed cells hypersensitivity • Decreased antibody response to new• Hypergammaglobuline antigens mia • Altered monocyte• Polyclonal activation function of B cells • Elevated level of immune complexes in serum
The National Family Health Survey conducted between 2005 and 2006 measured HIV prevalence among the general adult population of India Age group HIV prevalence (%) Male Female Total 15-19 0.01 0.07 0.04 20-24 0.19 0.17 0.18 25-29 0.43 0.28 0.35 30-34 0.64 0.45 0.54 35-39 0.53 0.23 0.37 40-44 0.41 0.19 0.30 45-49 0.48 0.17 0.33 Total age 15-49 0.36 0.22 0.28 NACO showed that by the end of 2005 the total number of reported AIDS cases in India was 116,905, of which 34,177 were women. Around a third of these were among people younger than 30 years. AIDS is pandemic.
Transmission of HIVTypes of exposure Approximate chance of infection per exposureUnprotected Sexual intercourse 0.1-1.0%Blood & blood products >90%Tissue & organ donation 50-90%Injection & surgicals 0.5-1.0%Mother to baby (MTCT) 30%
DiagnosisMainly 2 laboratoryadministration areemployed• Immunological tests• Specific tests/ serological tests/ HIV test
Immunological testsTotal leukocyte & lymphocyte count<2000/mm³T cell subset assay- T4:T8 ratio reversed• CD4+T cell count< 200/mm³Platelet count-thrombocytopeniaRaised IgG & IgA levelsDiminished CMI by skin testsLymph node biopsy
Specific tests (HIV test)Antigen detectionVirus isolation- CoculturetechniquePolymerase chain reactionAntibody detection: includesserological tests like• ELISA/EIA• Western blot test
ProphylaxisHealth educationProtected sexual relationshipSafe blood transfusionUse of sterile surgical equipments & needlesReplacement feeding & abortion (MTCT)Public awareness
Treatment Approaches to the treatment of AIDS includes The treatment & prophylaxis of Infections & tumours General management & rehabilitation Immunorestorative measures Specific anti HIV agents
HIV vaccinesAn AIDS vaccine does not yet exist, but efforts to develop avaccine against HIV and AIDS have been underway for manyyearsSince 1987, more than 30 vaccine candidates have beentestedAn AIDS vaccine could be effective in either of two ways• Preventive vaccine• Therapeutic vaccine
Pre exposure: Post-infection:Preventive vaccine Therapeutic vaccineProduct recombinant Product recombinant envelope vaccine envelope core protein Aim: to Aim: to immunize stimulate the against HIV immune infection with system to molecules redouble its copied from natural effort viral surface or to defeat HIV core
Developing an AIDS vaccine is a verydifficult challenge for scientists• Nobody has ever recovered from HIV infection, so there is no natural mechanism to imitate• HIV destroys the immune system cells that are meant to fight against it• Soon after infection, HIV inserts its genetic material into human cells, where it remains hidden from the immune system• HIV occurs in several subtypes, each of which is very different from the others• Within each subtype, HIV is highly variable and constantly changing• There are no good animal models to use in experiments
MicrobicideA microbicide is something designed to destroy microbes(bacteria and viruses) or to reduce their ability to establishan infectionA microbicide would share many of the advantages of anAIDS vaccineThe first microbicide candidates developed were made frombarrier gels, among them nonxoynol-9 and cellulose sulfate.More recent trials have been testing antiretroviral-basedmicrobicides, which aim to prevent HIV infection
A microbicide could work in at least four different ways:• Kill or inactivate HIV• Stop the virus entering human cells• Enhance the body’s normal defense mechanisms against HIV• Inhibit HIV replicationIt would be especially useful for womenAn effective microbicide must be made into acommodity that people will want to use regularly, suchas a cream, gel or vaginal ring.
Agents And Factors Responsible For Causing AIDS other than HIV AIDS in hemophiliacs relates to the use of corticosteroids and other immunosuppressive agents to prevent the development of antibodies. The chronic use of medications containing glucocorticoids at high doses by inhalation caused severe impairment of the immune defenses of the lungs and the upper respiratory tract. This led to the infection of the lungs and other organs with opportunistic microorganisms and the development of cancer
AIDS in Africa results from malnutrition, the consequent release of endogenous cortisol, and opportunistic diseases. Atrophy in the thymus and lymphoid tissue in people suffering from malnutrition has been known since 1925; malnutrition also impairs T cells functions. Kaposis sarcoma (KS), an AIDS-indicator disease, developed in HIV -negative patients chronically treated with glucocorticoids and people suffering from severe malnutrition.
Some myths about AIDS The virus being transmitted through mosquitoes which have bitten someone with HIV You CAN’T get HIV from coughing or sneezing and certainly not from swimming pools, showers or toilets In southern Africa, there was a belief that if a man has sexual intercourse with a virgin, it will cure his AIDS
The “gay plague” was seen as God’s disapproval of homosexuality which is described in the traditional Bible as a sin. It was the Almighty’s way of punishing gays for their “lewd” behaviour. Many people mistakenly believe that what destroys HIV in the test tube must also work in the human body. This is one reason why a number of disinfectants and other chemicals have been wrongly promoted as cures for AIDS like armenicum, colloidal silver etc.
Current researches on AIDSNational Institute of Medical Research where scientistshave discovered that a gene found in rhesus monkeys canprevent HIV. The same gene in humans can’t block thevirus but it appears that only one change is needed toenable it to do so. If this proves to be the case it would bea remarkable breakthrough in the search for a cureThere are various vaccine treatment strategies. Oneinvolves the injection of so-called "naked" DNA. The DNAcontains genes that code for gag, a viral componentthought to be critical to the development of AIDS
Highly Active Anti-Retroviral Therapy (HAART) consists drug mixturetypically contains a nucleoside analog, which blocks genetic replication,and inhibitors of two enzymes that are critical enzyme in the making ofnew virus (protease and reverse transcriptase).Clinical trials for phase one of the HIV/AIDS vaccine being developed inIndia is in final stage upto December 2010 with scientists fromTuberculosis Research Centre (TRC), Chennai, and National AIDS ResearchInstitute (NARI), PuneSecond phase of AIDS vaccine trials completed under internationalproject- Nov.2010Majority of the current research is focusing on the development ofantiretrovirals and improving their effectiveness.
Some key words Cell tropism: The property of particular organism to infect a particular cell is called cell tropism. Zoonosis: transmission of pathogens from animals to human SIVcpz: Simian immuno virus of chimpanzee Seroconversion: conversion of serotypes or antigenic variance Antigenic variation: the sequence of changes that occur frequently in the antigenic structure of the organism. Iatrogenic: man-made event Cytokines: a soluble substance which can communicate with other immune cells for the presence of antigens Chemokines: chemotactic cytokines
References www.wikipedia.org www.avert.com www.originofaids.com www.sciencedirect.com www.ehealthmd.com www.sciencedaily.com www.guide4living.com Textbook of microbiology- Bhatia & Ichhpujani Textbook of microbiology- Ananthnarayana & Paniker Immunology- Kuby Medical immunology- Gabriel Virella A textbook of microbiology- R.C.Dubey