Unit 4- HIV Flashcards

Question

What is Primary HIV- 1 Infection?

Answer 1

Period after infection but before the development of detectable antibodies against HIV-1 Illness resembles “mono” or the flu 50% are asymptomatic

Answer 2

Neither signs nor symptoms of the disease present This phase typically lasts an average of 10 years Typical progressors Rapid progressors (10-20%; AIDS within 5 yrs) Slow progressors (5-15%; AIDS free for \> 15 yrs) Long-term progressors (1%; no signs of disease) Frequency of opportunistic infections increases as CD4 T cell counts drop below 200 cells/mL

Answer 3

Without anti-retroviral therapy, the patient will die within 2–3 years. As T-lymphocyte counts decrease below 50 cells/µl, the number of opportunistic infections increases. AIDS patients also suffer from malignancies such as non-Hodgkin’s lymphoma. Wasting syndrome is also common- a loss of more than 10% of body weight due to fever or diarrhea for more than 30 days. AIDS patients are managed with antimicrobial prophylactic regimens.

Answer 4

HIV isolated in 1983 First commercial antibody detection tests were available in 1985. Today, most clinical labs screen for HIV-1 and HIV-2 using an ELISA test (specimen is a patient’s blood sample). All classes of anti-HIV antibodies are detected with these assays.

Answer 5

* Requires 2 doctor visits * #1. Blood drawing and pretest counseling * #2. Test results and additional counseling if needed * Performed by healthcare worker, tests results within 5–30 minutes * e.g., done on women in labor before delivery to determine infection status * patients following an accidental needle stick injury * “False negative” window- 3 weeks to 6 months between time of infection and test * 97% of people seroconvert by 3 months after infection * Positive ELISA tests must be confirmed by Western blot

Answer 6

* Confirmatory test to exclude false-positive results * Nitrocellulose membrane is probed with patient serum * If the patient has been exposed to HIV, + bands will be observed on the Western blot

Answer 7

* FDA approved first system in 1996 * Home Access HIV-1 Test System * Uses simple finger prick of blood sample * Place on filter paper * Mail in for laboratory testing * Confidential results obtained through toll-free phone number and post-test counseling is available

Answer 8

* ~ 1 in 4 of the 1 million Americans infected with HIV don’t know they are infected. * This group is most responsible for the spread of HIV. * CDC released voluntary testing guidelines in 2006 that would apply to every American, ages 13–64.

Answer 9

* HIV mutates rapidly * Three distinct groups of HIV-1 based on genetic similarities * M (Major) group * O (Outlier) group; W. Africa * N (New) group * M group is further divided into clades or subtypes: A, B, C, D, F, G, H and K * Two viruses of different subtypes can infect the same cell * Circulating recombinant forms (CRFs)

Answer 10

* Retroviridae family * Lentivirus genus (from Latin word lenti, for “slow”) * Cause slowly progressive, inflammatory diseases * HIV particles are 100–200 nm icosahedron-shaped sphere surrounded by an envelope * Envelope contains glycoproteins gp120 and gp41 spikes * Matrix proteins located below the envelope * Two copies of genome (+) ssRNA, cellular tRNAlys bound to each genome, which acts as a primer for RT * Reverse transcriptase (RT; p64) and integrase (p34) bound to viral genome * Protease (p10) also found within nucleocapsid of virus particle

Answer 11

* HIV infects CD4+ T lymphocytes and will lyse them during a productive infection. * HIV infects other cells but does not lyse them: * Natural killer cells * CD8+ killer T-cells * Macrophages * Cell of the nervous system (e.g., astrocytes, neurons, glial cells, and brain macrophages) * Dendritic cells

Answer 12

* Early course of infection: HIV infects macrophages * Later in the course of infection: HIV infects T lymphocytes * The rapid progression to AIDS is associated with a switch in co-receptor preference. * HIV enters cells via a cellular receptor and co-receptor * Major cellular receptor: CD4 present on T-lymphocytes (also present in low concentrations on macrophages) * Co-receptor on T lymphocytes: CXCR4 (fusion) Co-receptor on macrophages: CCR5

Answer 13

* gp120 of the virus interacts with CD4. * Subsequently, HIV gp120 and gp41 undergo a conformational change, causing a co-receptor reaction. * The virus anchors into the membrane of the CD4+ cell. * HIV gp41 changes into a coiled shape, bringing the virus and cell membrane together, allowing them to fuse, resulting in entry and uncoating.

Answer 14

* HIV RT binds to tRNAlys on the viral genome and initiates DNA synthesis * Refer to Chapter 10 (retroviral genome replication) * When reverse transcription is complete, the final product is dsDNA flanked by LTRs at each end of the viral genome. * The viral DNA is transported to the nucleus of the cell where the viral genome may be integrated into the host cell’s chromosomal DNA.

Answer 15

Proviral integration is catalyzed by the integrase (p32) protein. p32 is packaged in the original HIV particle. HIV can latently infect cells. T cells in the gut The latent reservoirs are one of the main barriers to elimination of HIV infection. During a production infection, HIV-1 is reactivated and the completion of the life cycle occurs.

Answer 16

HIV-1 utilizes the host cell’s transcription and translational machinery. The proviral DNA is transcribed from a single promoter in the 5′ LTR into a 9 kb viral RNA transcript by the cellular RNA polymerase II. HIV-1 tat and rev regulate gene expression.

Answer 17

* TAR is located at the 5′ end of all HIV RNAs. * The binding of tat to TAR increases the transcription rate from the HIV LTR at least 1000-fold. * rev binds to the RRE element, facilitating the export of unspliced and incompletely spliced viral RNAs from the nucleus to cytoplasm. * Some full-length viral mRNAs are packaged into virions following transport into the cytoplasm. * Other viral mRNAs are spliced within the nucleus to form mRNAs that are translated into the different viral proteins.

Answer 18

Cellular ribosomes translate proviral mRNA into viral proteins. Gag gene and the gag and pol genes together are translated into one large precursor polyprotein cleaved by a viral encoded protease. Full-length env, gp160 is transported through the Golgi where it is glycosylated and cleaved by a cellular protease into gp120 and gp41 to form mature envelope proteins. Mature gp120 and gp41 are targeted to the surface of the infected cell.

Answer 19

* HIV-1 virion components (e.g., the viral RNA, gag, pol, and env proteins) are assembled at budding sites located at the cellular plasma membrane. * The gag and gag-pol proteins are cleaved by an HIV specific protease to form mature virus particles.

Answer 20

* Destruction of virus-specific CD4 T helper cells * Antigenic escape variants * Hijacking of cellular complement inhibitors * HIV Nef downregulates expression of MHC class I * HIV Tat upregulates Bcl-2 in infected cells; prevents apoptosis * HIV can also trigger apoptosis to facilitate spread * New mechanisms continued to be discovered!

Answer 21

* Ultimately, HIV causes AIDS by depleting CD4+ T helper lymphocytes. * Weakening of the immune system * Body cannot stop infections or remove cancer cells * Opportunistic infections * HIV causes syncytia formation * AIDS dementia complex * Occurs in 20% of infected individuals * Symptoms: * Impairment of cognitive reasoning (e.g., short-term memory problems and concentration) * Behavior changes (apathy, withdrawal, irritability, depression, personality changes) * Motor performance (clumsiness, tremors, leg weakness)

Answer 22

* Individuals who are homozygous for a defective CCR32 gene are virtually resistant to HIV infection. * two defective copies are inherited, one from each parent * Individuals who are heterozygous for the defective CCR532 gene progress more slowly to AIDS * only one defective copy inherited

Answer 23

* CCR5 gene is missing 32 base pairs. * Codes for a truncated protein that is not detected on the cell surface * HIV gp120/gp41 cannot attach to it to infect cells

Answer 24

* European populations * 5%–14% heterozygous CCR532 * 1% homozygous in some populations such as Caucasian North Americans * The CCR532 allele is almost absent in African, Asian, Native American Indian, and Middle Eastern populations.

Answer 25

* Chemokine receptors play a central role in the immune response against many pathogens. * Time is needed for natural selection to increase the frequency of a rare allele. * People with CCR532 survive without immune system problems because other chemokines compensate for CCR5 (e.g., CXCR4 or CCR2). * Major infectious diseases in history (selective pressures) * Bubonic plague * Smallpox * Syphilis * Tuberculosis

Answer 26

* CCR532 led to increased survival during smallpox outbreaks that occurred in 14th century Europe. * During this time, smallpox outbreaks were ongoing, allowing for continuous natural selection. * The CCR532 genetic variant was an unintended but welcomed consequence of smallpox.

Answer 27

* CD4+ T Lymphocyte Counts * Less than 200 per µl plasma * Virus load monitoring * Used to make recommendations for antiviral treatment of patients * Measure HIV-1 RNA copies per ml of plasma * 100,000 copies per ml of plasma = clinical AIDS * An absence of detectable RNA copies suggests a slower progression to AIDS * **_Viral set point:_** viral load of person infected with HIV, which stabilizes after acute infection * Reached after immune system has developed HIV antibodies * The higher the set point, the faster the progression to AIDS * The lower the set point, the longer the disease remains in clinical latency

Answer 28

* Zidovudine (AZT), a thymine analog, RT inhibitor first approved HIV-1 treatment * Drug resistance to AZT emerged * 1996: David Ho * HAART, Highly Active Retroviral Therapy—use of at least 3 compounds simultaneously to block HIV RT, protease, entry/fusion, integrase, etc.

Answer 29

1. **Non-nucleoside (RTNNI) or nucleoside reverse transcriptase (RTNI)** inhibitors of HIV RT; addition of faulty nucleotides; competitive substrate inhibitors 2. **Protease inhibitors** that inhibit HIV maturation by blocking an HIV-specific protease, resulting in noninfectious virus 3. **Fusion inhibitors** that block HIV fusion of viral gp41 protein and the host cell membrane 4. **Integrase inhibitors** block HIV p32 activity, abolishing integration of the proviral DNA copy of HIV into the host cell chromosome 5. **CCR5 blocking inhibitor** block viral attachment

Answer 30

* Set point= viral load which stabilizes after acute HIV infection * Reached after development of antibodies * Higher the set point, the faster the progression to AIDS

Answer 31

* Still no HIV vaccine * An AIDS patient harbors 100 million genetically distinct variants of HIV. * HIV variants can escape both antibody and T-cell immune responses. * Will a vaccine be able to cope with this variability?

Answer 32

* HIV particles carry numerous host-derived proteins within the HIV envelope. * Many serum proteins are bound to the HIV particle. * Many of the original gp120 spikes have been lost. * This interferes with host antibody responses toward the virus.

Unit 4- HIV Flashcards

(57 cards)