HIV & AIDSPresented By:
CONTENTS Introduction of HIV           HIV vaccines History & origin              Microbicides Crossgenesis & systema...
HIVHuman Immunodeficiency VirusSimilar to SV40 & HTLVAn HIV particle is around 100-150 billionths of a meter in diameter.G...
HISTORYHIV probably transfers to humans in Africa between 1884 and 1924.The name “AIDS” – Acquired Immuno Deficiency Syndr...
OriginThe hunter theory• The most commonly accepted theory• SIVcpz was transferred to humans as a result of  chimps being ...
The hepatitis B theory• chimpanzees, contaminated with numerous viruses,  were used to produce hundreds of hepatitis B vac...
CROSS GENESISHIV-2 corresponds to SIVsm, a strain ofthe Simian Immunodeficiency Virusfound in the sooty mangabey, which is...
FamilyRETEROVIRIDAE   SUB FAMILY LENTIVIRINAE    Subgroup LENTIVIRUS
Generalized Structure of HIV Viral envelope (lipid membrane) 72 little spikes, which are formed from the    proteins gp1...
Envelope  Matrix layer  CapsidReversetranscriptase
Antigenic variation & diversity Highly mutable virus Exhibits frequent antigenic variation as well as  differences in ot...
Antigenic structure HIV has 3 antigen types:   Envelope antigen- glycosylated polyproteins & antibodies to    these prot...
GroupsVirus   Types                (subtypes)                      M                (A, B, C, D, F,                  G, H,...
Genome of HIVHIV has following genes• Genes coding for structural proteins-  • Gag, pol, env• Genes coding for non structu...
Genes coding for structural proteins gag- determines the core & shell of the virus   P17, P 24, P55 pol- codes for the ...
 Vif- viral infectivity factor gene influences the infectivity of    viral particles.   Vpr- stimulates the promoter reg...
1. ADSORPTION2. PENETRATION3. REVERSETRANSCRIPTIONLIFE CYCLE OF
4. INTEGRATION5. TRANSCRIPTION6. ASSEMBLY& RELEASE                   LIFE CYCLE OF
1. ADSORPTION2. PENETRATION3. REVERSETRANSCRIPTION4. INTEGRATION5. TRANSCRIPTION6. ASSEMBLY& RELEASELIFE CYCLE OF
HIV and the Immune SystemWhen infection occurs through a mucosal surface, the virus is taken up bysubmucosal Langerhans ce...
The infection of monocytes, macrophages, andrelated cells is productive but not cytotoxic, andthe infected cells become a ...
On the negative side, enhancing antibodies, whichreact with gp41 antibodies and enhance HIVinfectivity by an unknown mecha...
Monocytes, macrophages, dendritic                                        cells                                            ...
Stages of HIV infection4 stages of HIV infectionPrimary: No symptoms at allAsymptomatic :• Lasts for an average of ten yea...
Clinical Features of HIV InfectionThe natural course of HIV infection is as follows:  1. Seroconversion illness  2. Incuba...
4. AIDS• Opportunistic  Infections• Opportunistic Tumors• Neurological  manifestations• Dermatological  Manifestations• Ga...
Opportunistic Infections Protozoal                          Bacterial   Pneumocystis carinii               Mycobacteri...
 Opportunistic Tumors   Burkitts lymphoma   Burkitts-like lymphoma   Diffuse      large     B-cell    lymphoma (DLBCL)...
Neurological              Dermatologicalmanifestations            manifestations• Organic Psychosis And   • oral hairy leu...
Immunological abnormalitiesFeatures that             Other featurescharacterizes AIDS• Lymphopenia             • Decreased...
Epidemiology
 The National Family Health Survey conducted between 2005 and 2006  measured HIV prevalence among the general adult popul...
Transmission of                                      HIVTypes of exposure                       Approximate chance of infe...
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<...
Specific tests (HIV test)Antigen detectionVirus isolation- CoculturetechniquePolymerase chain reactionAntibody detection: ...
ProphylaxisHealth educationProtected sexual relationshipSafe blood transfusionUse of sterile surgical equipments & needles...
Treatment            Approaches to the treatment of                    AIDS includes                                    Th...
 Specific anti-HIV agents  Integrase Inhibitors- Isentress  Entry Inhibitors- Fuzion  Non-Nucleosides Reverse Transcri...
HIV vaccinesAn AIDS vaccine does not yet exist, but efforts to develop avaccine against HIV and AIDS have been underway fo...
Pre exposure:         Post-infection:Preventive vaccine    Therapeutic vaccineProduct recombinant   Product recombinant en...
Developing an AIDS vaccine is a verydifficult challenge for scientists• Nobody has ever recovered from HIV infection, so  ...
MicrobicideA microbicide is something designed to destroy microbes(bacteria and viruses) or to reduce their ability to est...
A microbicide could work in at least four different ways:• Kill or inactivate HIV• Stop the virus entering human cells• En...
Agents And Factors Responsible For                Causing AIDS                other than HIV AIDS in hemophiliacs relates...
 AIDS in Africa results from malnutrition, the consequent release  of endogenous cortisol, and opportunistic diseases. At...
Some myths about AIDS The virus being transmitted through mosquitoes which have  bitten someone with HIV You CAN’T get H...
 The “gay plague” was seen as God’s disapproval of  homosexuality which is described in the traditional Bible as a sin.  ...
Current researches on AIDSNational Institute of Medical Research where scientistshave discovered that a gene found in rhes...
Highly Active Anti-Retroviral Therapy (HAART) consists drug mixturetypically contains a nucleoside analog, which blocks ge...
Some key words Cell tropism: The property of particular organism to infect a    particular cell is called cell tropism. ...
References www.wikipedia.org www.avert.com www.originofaids.com www.sciencedirect.com www.ehealthmd.com www.scienced...
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HIV & AIDS- RAHUL SAHU
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HIV & AIDS- RAHUL SAHU

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  • LAV – lymphoadenopathy associated virusHTLV- human T leukemia virus
  • Antibody dependent cell cytotoxicity
  • Cmv cytomegalo virusHsv herpes simplex virusVzv varicella zostervirus
  • HIV & AIDS- RAHUL SAHU

    1. 1. HIV & AIDSPresented By:
    2. 2. 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
    3. 3. 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.
    4. 4. 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
    5. 5. 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.
    6. 6. 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
    7. 7. CROSS GENESISHIV-2 corresponds to SIVsm, a strain ofthe Simian Immunodeficiency Virusfound in the sooty mangabey, which isindigenous to western Africa.
    8. 8. FamilyRETEROVIRIDAE SUB FAMILY LENTIVIRINAE Subgroup LENTIVIRUS
    9. 9. 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.
    10. 10. Envelope Matrix layer CapsidReversetranscriptase
    11. 11. 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
    12. 12. 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.
    13. 13. GroupsVirus Types (subtypes) M (A, B, C, D, F, G, H, J, K) O HIV 1 NHIV P HIV 2 No data
    14. 14. 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
    15. 15. 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
    16. 16.  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
    17. 17. 1. ADSORPTION2. PENETRATION3. REVERSETRANSCRIPTIONLIFE CYCLE OF
    18. 18. 4. INTEGRATION5. TRANSCRIPTION6. ASSEMBLY& RELEASE LIFE CYCLE OF
    19. 19. 1. ADSORPTION2. PENETRATION3. REVERSETRANSCRIPTION4. INTEGRATION5. TRANSCRIPTION6. ASSEMBLY& RELEASELIFE CYCLE OF
    20. 20. 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.
    21. 21. 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.
    22. 22. 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.
    23. 23. 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
    24. 24. 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
    25. 25. 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
    26. 26. 4. AIDS• Opportunistic Infections• Opportunistic Tumors• Neurological manifestations• Dermatological Manifestations• Gastrointestinal Manifestations• Manifestations in children and during pregnancy
    27. 27. 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
    28. 28.  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
    29. 29. Neurological Dermatologicalmanifestations manifestations• Organic Psychosis And • oral hairy leucoplakia Complete Dementia • itching maculopapular eruption• Subacute Encephalitis • Seborrhoeic eczema• Acute meningoencephalitis, • allergic exanthemas and acne like eruptions Aseptic meningitis • Herpes zoster, Cobdylomata acuminatum, Verruca vulgaris, Molluscum contagiosum• Peripheral neuropathy
    30. 30. 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
    31. 31. Epidemiology
    32. 32.  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.
    33. 33. 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%
    34. 34. DiagnosisMainly 2 laboratoryadministration areemployed• Immunological tests• Specific tests/ serological tests/ HIV test
    35. 35. 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
    36. 36. Specific tests (HIV test)Antigen detectionVirus isolation- CoculturetechniquePolymerase chain reactionAntibody detection: includesserological tests like• ELISA/EIA• Western blot test
    37. 37. ProphylaxisHealth educationProtected sexual relationshipSafe blood transfusionUse of sterile surgical equipments & needlesReplacement feeding & abortion (MTCT)Public awareness
    38. 38. Treatment Approaches to the treatment of AIDS includes The treatment & prophylaxis of Infections & tumours General management & rehabilitation Immunorestorative measures Specific anti HIV agents
    39. 39.  Specific anti-HIV agents  Integrase Inhibitors- Isentress  Entry Inhibitors- Fuzion  Non-Nucleosides Reverse Transcriptase Inhibitors (NNRTIs)- Intelence, AZT (Zidovudine) etc.  Nucleotide Analogs- Vireads  Protease Inhibitors (PIs)- Prezista  Nucleoside Reverse Transcriptase Inhibitors (NRTIs)- Retrovir etc.  Combination Medications- Combivir  Hydrea - Hydroxyurea
    40. 40. 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
    41. 41. 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
    42. 42. 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
    43. 43. 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
    44. 44. 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.
    45. 45. 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
    46. 46.  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.
    47. 47. 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
    48. 48.  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.
    49. 49. 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
    50. 50. 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.
    51. 51. 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
    52. 52. 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
    53. 53. Back tocontents

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