MICR J210 1st Edition Lecture 22Outline of Last Lecture I. Poliovirus: PoliomyelitisII. Rhinovirus: Common coldIII. Coxsackievirus and EchovirusesIV. Influenza virus: FluV. Respiratory syncytial virus (RSV)VI. Mumps virus: MumpsVII. Measles virus: MeaslesVIII. Rubella virus: German measlesIX. Rhabdovirus: RabiesX. ArbovirusXI. RotavirusXII. NorovirusXIII. Ebola VirusOutline of Current Lecture 1. Human Immunodeficiency Virus2. Hepatitis Virusesa. Hep Ab. Hep Ec. Hep Bd. Hep Ce. Hep DCurrent LectureHuman Immunodeficiency virus (HIV)- In 1985, the first description of acute human immunodeficiency virus (HIV) infection, a "mononucleosis-like" illness, was publishedo ss RNA-containing, enveloped viruso Two serotypes: o HIV-1 (Europe, Central Africa and the Americas)o HIV-2 (West Africa) and India- HIV Infectiono HIV infection is usually acquired through sexual intercourse, exposure to contaminated blood, or perinatal transmissiono Transmitted via genital, anal, and oral sex o HIV has several targets including dendritic cells, macrophages, & CD4+ T cellsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.o Interstitial dendritic cells are found in cervicovaginal epithelium, rectal, as well as tonsillar and adenoidal tissue, which may serve as initial target cells in infection  HIV-1 is captured by the Dendritic Cells and delivered to the lymph node where the virus is transmitted to CD4+ T cells. The lymph node then becomes the principal site of virus productiono RNA --> DNA --> Host Cell DNA (macrophages/lymph nodes), also in resting (memory) T-lymphocytes - incubation period of 200 days to 20 years Virus binds to cells that have the CD4 antigen (1st receptor) Virus also requires a 2nd receptor:  CXCR4 (or Fusin) for T-cell tropic, or CCR5 for M-cell tropic- Approximately 1% of the Caucasian population are naturally resistant to HIV-1 infection because of a mutation in the CCR5 geneo In order for HIV to enter, GP-120 must bind to the chemokine receptor (CXCR4 on the surface of T helper cells or CCR5 on the surface of macrophages) in addition to CD4 molecule- Steps of HIV Replicationo Binding and entryo Reverse Transcriptiono Integrationo Transcriptiono Assemblyo Release- Pathogenesis of HIVo At the time of initial infection with HIV, patients have a large number of susceptible CD4+ T cells and no HIV-specific immune response. o HIV destroy or disable CD4+ T cells in an HIV infected individual by several mechanisms: Direct killing of CD4 cells by HIV - gp120 – Lysis Syncytia formation between infected and uninfected cells Induction of apoptosis in infected cells. Infected CD4+ T cells are killed when cellular regulation is distorted by HIV proteins, leading to their suicide by a process known as programmed cell death or apoptosis Cytotoxic cell responses to infected CD4 cells and kills them- Virus produces a slow but progressive deterioration in the host immune system, and in its most advanced stages is complicated by opportunistic infections, neurologic disorders, and some forms of cancero During primary infection, HIV disseminates widely through the body, usually accompanied by an abrupt decrease in CD4+ T cells. An immune response to HIV ensues,with a detectable decrease in viral load. Clinical latency follows but CD4+ T cells slowly continue to decrease until they fall to a critical level below which there is a substantial risk of opportunistic infections- HIV Clinical Pictureo 6 stages of the disease: Stage 1: 6 mo-1 yr, antibodies in blood: fever, headache, fatigue: T-cell count normal ~ 800/mm3 Stage 2: 3 - 5 yrs, usually no symptoms except for swollen lymph glands, active viral replication, 3-100 billion/day: host immune system able to handle! Stage 3: 1 - 2 yrs, CMIR is severely impaired, T-cell count drops to <400/mm3  Stages 4 & 5: 1 - 2 yrs, T-cell count is usually <200/mm3, "OPPORTUNISTIC INFECTIONS” become a problem Stage 6: 1 - 2 yrs after stage 5, total loss of T4 cell function, severe weight-loss, dementia, unable to walk or talk, 'waste away'-Opportunistic Infectionso The problem is about 60 different opportunistic infections which all should be treated Yeast infections like Candidiasis (thrush), bacterial and viral infections - very common because of low-immunity Pneumocystis jiroveci (carinii), Fungus ~70% of AIDS deaths Mycobacterium tuberculosis Reactivation of latent herpes viruses –i.e.: HSV and CMV Kaposi's sarcoma - HHV-8 Encephalitis (dementia)- Prevalenceo More than 95% are in developing countrieso 2000 are in children under 15 years of ageo About 12,000 are persons aged 15 to 49 years, of whom: almost 50% are women about 50% are 15–24 year olds- Treatmento Azido-dideoxythymidine (AZT), first drug treatment Inhibits viral genomic replication, side effects virus resistance, toxicity (kids=legs swelling)o Protease inhibitors (PI’s) inhibit maturation of viral particles. Examples of commercially available: Saquinavir, Ritonavir, Indinavir, Viracepto HAART=Highly Active Antiretroviral Therapy A combination of AZT+2 PI’s- HAART works by suppressing the virus and decreasing the rate of opportunistic infections.- HAART may cause unpleasant side effects in some patients- People infected with HIV who take antiretroviral drugs can still transmit HIV to others through unprotected sex and needle-sharing.- In some countries (especially in Africa) there is social resistance to Western-style HIV therapy.- Preventiono No vaccine yet Avoid sexual contact with people at risk. "NOT A GAY DISEASE ANYMORE” Use condoms (not 100% safe) - Of 2000 people in the US with more than one partner surveyed, Only 17% used condoms on a regular basiso Avoid dirty needles and needle-sharing Screen blood and blood products for HIV before transfusion, avoid high-risk blood donorso Abstinence best - single, faithful partnero Healthcare personnel Should assume that the blood and other body fluids from all patients are potentially infectious. They should therefore follow infection control precautionsat all times Routinely use barriers (such as gloves and/or goggles) when anticipating contact with blood or body fluids  Wash hands and other skin surfaces immediately after contact with blood or body fluids. Decontaminate all waste material Carefully handle and dispose