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Lectures 21, 22, 23, and 24

by: Nathaniel Bautz

Lectures 21, 22, 23, and 24 MICROBIO 160

Marketplace > University of Massachusetts > Biology > MICROBIO 160 > Lectures 21 22 23 and 24
Nathaniel Bautz
GPA 2.9
MICROBIO 160 - Biology of Cancer and AIDS
Mitchell Walkowicz

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Here are the notes for lectures 21,22, 23, and 24.
MICROBIO 160 - Biology of Cancer and AIDS
Mitchell Walkowicz
Class Notes
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This 5 page Class Notes was uploaded by Nathaniel Bautz on Friday April 10, 2015. The Class Notes belongs to MICROBIO 160 at University of Massachusetts taught by Mitchell Walkowicz in Spring2015. Since its upload, it has received 101 views. For similar materials see MICROBIO 160 - Biology of Cancer and AIDS in Biology at University of Massachusetts.

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Date Created: 04/10/15
LECTURE 21 THE BIOLOGY OF HIV 0 90 O 90 O 90 O 90 What are Viruses gt A virus particle or virion consists of the following I Nucleic acid Genetic instructions either DNA or RNA either single stranded or double stranded I Coat of protein Surrounds the DNA or RNA to protect it I Lipid membrane Surrounds the protein coat found only in some viruses including in uenza enveloped viruses as opposed to naked viruses What Type of Virus is HIV gt Human immunodeficiency virus HIV is a lentivirus a member of the retrovirus family gt Lentiviruses are transmitted as enveloped RNA viruses gt Upon target cell entry viral RNA is converted to dsDNA by a virally encoded reverse transcriptase present in the virus particle What Does HIV look like gt An HIV particle is around 100150 billionths of a meter in diameter That s about the same as I 01 microns I 4 millionths of an inch I One twentieth of the length of an E coli bacterium I One seventieth of the diameter if a human CD4 white blood cell aj or Viral Components Gp120 Gp41 Viral envelope P17 P24 Protease Reverse transcriptase RNA Dynamics of Cell Entry gt Up to 90 of newly transmitted HIV uses CCR5 Mtropic gt R5 viruses are more often transmitted sexually gt CXCR4tropic virus emerges in 5060 of infected individuals within 5 years gt X4tropic Ttropic virus associated with pronounced depletion of CD4 T cells Understanding HIV Tropism gt Lower CD4 counts and higher viral load is seen with dual or mixed tropic virus compared to pure R5 or X4 gt X4 virus correlates with syncytia formation gt X4 virus associated with more rapid progression to AIDs CCR5 Delta32 mutation amp Resistance to HIV gt 1 of Europeans and even more in northern Europe inherit the CCR5 mutation from both parents making them resistant to HIV infection M gt gt gt gt gt gt gt gt gt gt gt gt gt gt 10 to 15 of Europeans carry a mutation from 1 parent making it more difficult but not impossible for them to become infected quotelite controllers maintain very low viral load without ART People of African Asian and South American descent almost never carry it 0 Berlin Patient Still HIV free 4 years after Bone Marrow Transplant Timothy Ray Brown a 40yearold man received 2 bone marrow transplants for acute myeloid leukemia Donor had a double or homozygous CCR5delta32 mutation The patient was 39conditioned39 by intensive chemotherapy and radiation prior to transplantation Successful reconstitution of CD4T cells in blood and gut without any trace of HIV The last direct evidence of HIV was detectable on day 60 after transplantation 393 Cell Types Infected by HIV gt gt gt gt Tlymphocyte NKT cell Macrophage NK cell CD4 LECTURE 22 HIV TESTING 393 When to Have an HIV Test gt CDC recommends people should have an HIV test if they fall into one or more of the following categories I Having three or more sexual partners in the last 12 months I Have received a blood transfusion prior to 1985 or have a sexual partner who received a transfusion and later tested positive for HIV I Not sure about one39s sexual partner39s risk behaviors I Being a male who has had sex with another mal I Using street drugs by injection especially when sharing needles andor other equipment I Having a sexually transmitted disease STD I Being a healthcare worker with direct exposure to blood on the job 393 HIV Mandatory Testing in the US gt Current US laws enforce mandatory testing for the following populations I Blood and organ donors I Military applicants and active duty personnel I Federal and state prison inmates under certain circumstances I Newborns in some states 393 Types of HIV Tests gt There are three broad categories of HIV tests I Screening tests I Confirmatory test I Tests of HIV progression and tropism 393 New HIV Test AB only tests miss up to 10 of HIV infections in some high risk populations Detects the HIV p24 antigen direct presence of HIV The most sensitive thirdgeneration antibody tests will pick up about 42 of acute phase infections whereas the new combination assay picks up about 90 of those in the acute phase Abbott Senior Director Gerald Schochetman 393 HIV Resistance and Tropism Test Resistance decreases the ability of drugs to control HIV amp affects treatment options Genotype test Checks for mutation in HIV that cause drug resistance Phenotype test challenges virus with all HIV drugs in a test tube Virtual phenotype test genotype test that uses phenotype information to predict which drugs will be effective against HIV and its mutations VVV VVVV LECTURE 23 HIV TRANSMISSION 393 Transmission of HIV gt The most common methods of transmission of HIV are I Unprotected sex with an infected partner I Sharing needled with infected person gt Almost eliminated as risk factors for HIV transmission are I Transmission from infected mother to fetus I Infection from blood products 393 Patient Zero and HIV Transmission Ga tan Dugas A Canadian who worked for Air Canada as a ight attendant Claimed to have had over 2500 sexual partners across North America since 1972 Diagnosed with Kaposi39s Sarcoma in June 1980 In 1982 the CDC linked him to 9 of the first 19 cases in Los Angeles 22 cases in NYC and 9 more in 8 other cities Total of 40 of the first 248 cases in the US 393 Drug Use Alcohol and HIV Infection gt Alcohol use is associated with highrisk sexual behaviors and injection drug use two major modes of HIV transmission 393 HIV Transmission Risk and Sexual Behavior gt Transmission depends on HIV viral load and type of sexual behavior gt The relative risk for HIV transmission varies from 100 for receptive anal sex 20 for receptive vaginal sex 13 for insertive anal sex 10 for insertive vaginal sex to 2 for receptive fellatio versus 1 for insertive fellatio gt HIV transmission by oral sex between men has been reported gt HIV transmission is reduced by approximately 80 with condom use VVVV LECTURE 24 HIV PROGRESSION TO AIDS 393 Viral and Host Factors In uencing the Progression of AIDS gt Viral load the amount of virus in the blood of an HIVinfected person gt Most individuals with a rapid progression to AIDS have viruses that replicate rapidly and are more cytopathic with a wide cellular host range gt Antibodies that enhance virus infection can permit HIV spread to several different cell types including lymphocytes macrophages and fibroblasts gt Cellular immune responses can destroy virusinfected cells or suppress virus release via the production of antiviral cytokines or mechanisms involving cell cell interaction New AIDS Definition 1993 gt Cases peaked with the 1993 expansion of the case definition and then declined CD4 T Cells Cervical Cancer Pulmonary TB and recurring pneumonia were added as AIDS defining illnesses The most dramatic drops in both cases and deaths began in 1996 with the widespread use of combination antiretroviral therapy The CDC s Definition of AIDS gt All HIVinfected people with fewer than 200 CD4 T cells per cubic millimeter of blood compared with CD4 T cell counts of about 1400 for healthy people or gt His or her CD4 cells account are fewer than 14 percent of all lymphocytes gt That person has been diagnosed with at least one or more of the two dozen AIDS associated conditions that result from HIV39s attack on the immune system The Stages of HIV Infection gt STAGE 1 Primary HIV Infection short ulike illness large amount of HIV in the peripheral blood seroconversion HIV antibodies and cytotoxic lymphocytes gt STAGE 2 Clinically Asymptomatic Stage lasts for an average of ten years free from major symptoms there may be swollen glands HIV level in peripheral blood drops to very low levels patient remains infectious T helper cell infection gt STAGE 3 Symptomatic HIV Infection Over time the immune system loses the struggle to contain HIV lymph nodes and tissues become damaged HIV mutates and becomes more pathogenic T helper cell destruction emergence of opportunistic infections such as Oral Candidiasis thrush or hairy cell leukoplakia gt STAGE 4 Progression from HIV to AIDS As the immune system becomes more and more damaged the illnesses presented become more and more severe leading eventually to an AIDS diagnosis CD4 cell count below 200mm3 opportunistic infections Progression to AIDS gt Progression to AIDS is more rapid under the following circumstances I When Syncytia forming HIV is present I When acute infection is symptomatic I When HIV infection occurs with a drug resistant strain I When a higher set point of HIV RNA follows initial viremia after infection I When patient smokes I When opportunistic infections or neoplasms are present I When in congenital cases there are signs of infection less than 3 months of age Tuberculosis and HIV gt 13 persons living with HIV infection are coinfected with TB gt TB is the leading cause of death among people living with HIV in Africa gt TB is the cause of death for as many as 50 of all persons with AIDS HIV Elite Controllers gt HIVinfected individuals with asymptomatic HIV infection gt long term control of virus to undetectable or nearly undetectable levels gt Elite controllers have a rare set of genes that allow their immune systems to unleash killer T cells CD8 T cells With a greater ability to kill Viruses Elite Controllers EC gt EC S 1 of HIV gt Maintain durable HIV control to lt50 copiesmL Without HAART gt Rarely progress gt Also known as HIV controllers Definitions LTNP gt Definition is based on immunologic control ie stability of CD counts and duration of follow up I Clinically immunologically stable for duration of 710 years Without HAART Plasma Virus load is usually lt2000 HIV RNA copiesmL Symptomfree Incidence among HIV persons approx 5 Most ultimately manifest deterioration in CD4 counts Possible Virologic and host factors involved in HIV control gt Virus I Mutationsdefective Virus I Vital Fitness gt Host I Genetics I AntiViral host restriction factors I Immune response VVVV


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