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101 Cards in this Set
- Front
- Back
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What genera of retroviruses does HIV belong to?
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Lentivirus
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What enzyme is unique to retroviruses?
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Reverse Transcriptase
Of the RNA viruses, Retroviridae is the only family of RNA viruses to use a reverse transcriptase Of the DNA viruses, Hepadnaviridae is the only family of DNA viruses to use a reverse transcriptase |
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What is the role of reverse trancriptase?
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To convert a single-stranded RNA viral genome into a double-stranded DNA genome
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Why are mutations common with reverse transcriptase?
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The enzyme is "sloppy"
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What is the implication of a sloppy enzyme?
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Development of resistance secondary to increased mutation rate requiring changes in pharmacotherapy, e.g., triple-therapy drug regimens
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What are two identified serotypes of HIV responsible for?
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HIV-1 is responsible for AIDS
HIV-2 is responsible for a similar illness, but overall has milder clinical manifestations. |
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What is the general structure of retroviruses?
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An enveloped virus with a positive single-strand RNA genome.
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Waht is the viral envelope make from?
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Host cell membrane
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What are two surface glycoproteins found on te HIV envelope?
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1) Transmembrane glycoprotein (TM; fusoin protein, and gp31)
2) Surface glycoprotein (SU; attachment protein, and gp120) |
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Which surface glycoprotein is a TM (fusion) protein?
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gp41
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Which surface glycoprotein is a surface (attachment) protein?
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gp120
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What additional protein is found on the HIV enveloope?
Where? What is it involved with? |
Outer matrix protein (MA; p17)
Between the envelope and the capsid Entry of the DNA provirus into the nucleus and virus assembly |
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What is the capsid geometry of HIV?
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Comple, cone-shaped geometry
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What is the major capsid protein?
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p24
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Can p24 be used to detect HIV infection?
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YES
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When during teh course of HIV is p24 expressed?
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Throughout the infection
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What are the five components of the HIV capsid?
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1) Two identical copies of positive ssRNA genome
2) Nucleocapsid proteins 3) Reverse transcriptase 4) Protease 5) Integrase |
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What is p7?
What is its role? |
Nucleocapsid protein
To complex with RNA within the capsid |
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What are the three major HIV genes?
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gag
pol env |
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What does the gag gene code for?
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Core proteins
Matrix proteins |
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Which does the pol gene code for?
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Reverse transcriptase
Integrase Protease Ribonuclease |
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What are four additional coding regions found in teh HIV genome?
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U5
U3 R sequence Long terminal repeats |
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What is U5?
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Sequence of viral RNA found at the 5' end which contains part of the site needed for viral integration into the host cell chromosome and contains the transfer RNA primer binding site for reverse transcriptase.
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What is U3?
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The sequence of viral RNA at the 3' end which contains sequences used for control of transcription of the DNA provirus
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What is the R sequence?
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The repeated sequence of viral RNA found at both ends which is used during reverse transcription
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What are long terminal repeats?
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Two identical repeats that result from the duplication of the U and R units during the synthesis of the DNA provirus
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What are six steps of HIV replication?
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1) Binding to host cell receptor
2) Viral entry 3) Reverse transcription 4) Integration into host cell DNA 5) Transcription and translation 6) Assembly and maturation |
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Which three steps of HIV replication are dependent on viral proteins?
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Viral entry
Reverse transcription Integration |
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What parts of HIV replication require use of host cell machinery?
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Synthesis of viral genomes, messenger RNA, and structural proteins
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Which host cell receptor does HIV show tropism for.
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CD4 receptors
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What are four types of cells that contain CD4 receptors?
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1) T-helper cells
2) Lymphocytes 3) Macrophages 4) Dendritic cells |
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Which cell type is usually the first cell to become infected?
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Macrophages
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What is a chemokine receptor?
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Protein involved in the control of the immune response and inflammation
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Is there only one type of chemokine receptor?
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NO
In fact different HIV strains prefer certain chemokine receptors over others |
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What occurs if HIV binds the chemokine receptor?
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Fusion between teh viral envelope and the cell membrane secondary to envelope glycoprotein (TM) activation
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What host cell component serves as a primer for the initiation of reverse transcription?
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tRNA, which binds a specific viral RNA sequence
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What is the first product of reverse transcription?
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A DNA-RNA hybrid
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Which enzyme is involved in creating DNA from RNA?
What is another one of its roles? |
Reverse transcriptase
It has RNAse activity which degrades the DNA-RNA hybrid's RNA while concurrently synthesizing the DNA strand. |
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What is the double stranded DNA molecule end product called?
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The provirus
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What protein then helps with the transport of the provirus to the nucleus?
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Matrix protein (MA)
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What enzyme then cleaves chromosomal DNA and inserts the proirus into the host genome?
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Integrase
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Is the insertion and integration of the provirus random?
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YES
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What are the two genomic forms of HIV?
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+ssRNA (extracellular)
dsDNA (proviral, intracellular) |
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Which enzyme transcribes the integrated provirus into full length mRNA?
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Host cell RNA polymerase II
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What are the three basic products of the mRNA transcribed from the virus?
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Genome for viral pogeny
Gag proteins and gag-pol polyproteins Spliced RNA |
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What is a gag-pol polyprotein?
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The source of viral revere transcriptase adn integrase
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How is gag-pol polyprotein formed?
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In the process of translating a gag protein precursor, approximately 5% of the time the stop codon is missed, resulting in a gag-pol polyprotein
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What omponents combine with each other during HIV assembly?
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The genomes, uncleaved gag and gag-pol polyproteins, associate with the envelope glycoprotein (TM)-modified plasma membrane
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How does the plasma membrane become associated with the env glycoproteins?
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The env polyproteins are cleaved into SU and TM proteins by the golgi apparatus, which is subsequently transorted to the host cell membrane
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When is the viral protease that cleaves the gag and gag-pol polyproteins activated?
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As the virion buds from the surface of infected cells
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Which cell dies as a result of release of mature virions?
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Lymphocytes
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Which cell lives even after release of mature virions?
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Macrophages
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What are the four major routes of transmission of HIV?
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Sexual contact
Blood transfusion Contaminated needles Perinatal transmission |
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Is HIV present in both semen and vaginal secretions?
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YES
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Can other STDs increase the rate of transmission of HIV?
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YES
Any disease that compromises the integrity of the skin can facilitate transmission |
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What types of transfusions have resulted in HIV transmission?
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All types resulting in the screening of the blood supply for the presence of HIV
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What are three methods of HIV perinatal transmission?
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Transplacentally
Passage of baby through the birth canal Breast feeding |
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What can prevent perinatal transmission?
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Azidothymidine (zidovudine, AZT)
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What are three general ways in which HIV leads to clinical manifestations?
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Induction of an immnodeficient state
Host response to HIV-infected cells Destruction of cells by virus |
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What percent of HIV-postive individuals take more than 20 years to develop AIDS?
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10%
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What unique finding was found to decrease the likelihood of acquiring HIV in Kenyan prostitutes?
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Homozygously altered HIV coreceptors
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Where does the virus usually proliferate to after the initial infection?
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CD4+ T cells, macrophages, and dendritic cells
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How do CD4+ lymphocytes generally become infected?
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By contacting infected follicular dendritic cells in the germinal centers of lymph nodes.
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What percent of HIV+ individuals suffer from an acute, mononucleosis-like viral illness several weeks after being first infected?
What symptoms do these people report? |
33-66%
Patients are rarely diagnosed during the acute viral illness Fever, malaise, lymphadenopathy, and pharyngitis |
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What occurs during the acute viral illness?
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High rate of HIV replication in CD4+ lymphocytes leading to high levels of HIV (viremia) and presence of p24
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What is the response to the acute phase viremia?
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HIV-specific cytotoxic T cells respond, followed by the humoral response 1 to 10 weeks after intitial infection; this decreases the viral load and helps resolve the symptoms
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Does viral replication cease after the acute viral illness resolves?
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NO
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What is 'latent' during the latent period?
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Clinical symptoms
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What is not "latent" during the latent period?
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Viral replication
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What gradually results in a net loss during the latent period?
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CD4+ T cell count
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Why does the CD4+ T cell count only drop a little during the majority of the latent period?
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Stem cell output compensates
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What percent of HIV proviruses are transcriptionally inactive during the latent period?
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90%
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Why are there viremic episodes during the latent period?
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When the person becomes infected by other pathogens.
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What are some of the possible clinical manifestations of HIV during the latent period?
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Generalized lymphadenopathy, fevers, weight loss, and diarrhea, as well as bouts of herpes zoster and candidiasis.
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Generally speaking, what speeds the progression of HIV to AIDS?
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A stimulus, e.g., infection, activating resting T cells, inducing HIV replication, increasing the chance for mutations, and promoting syncytium formation
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What is a syncytium in the context of HIV?
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Uninfected cells that become directly infected by an infected cell.
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Do T-cell precursors get infected?
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Yes
and they eventually die |
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What is the problem with HIV mutations in terms of containing the infection?
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Decreased ability of antibodies and cytotoxic T cells to detect new antigens.
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When is a patient said to have AIDS?
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CD4 count <200/mL with serologic evidence of HIV and/or the appearance of one or more AIDs-defining illnesses.
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What cells play a key role in spreading HIV to other organs?
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Macrophages
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What is responsible for AIDS encephalopathy?
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Macrophages are responsible, not a decreased in CD4+ cells.
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How are macrophages linked with the wasting syndrome seen in AIDS?
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Likely by the release of cytokines such as tumor necrosis factor
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Are the eye, skin, and bone marrow infected by HIV?
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YES
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What are the malignancies commonly associated with AIDS?
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Kaposi sarcoma
Lymphoma |
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What are the common bacterial opportunistic infections associated with AIDS?
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Mycobacterium avium complex (MAC)
Tuberculosis Streptococcus pneumoniae Salmonella |
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What are the common viral opportunistic infections associated with AIDS?
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1) Herpes simplex virus (HSV-1 and HSV-2)
2) JC virus 3) Epstein-Barr virus 4) CMV 5) Kaposi sarcoma (human herpesvirus 8 [HHV-8]) |
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What virus is commonly associated with chrioretinitis?
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CMV
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What are the common fungal, parasitic, and protozoan opportunistic infections associated with AIDS?
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1) Candida
2) Cryptococcus 3) Pneumocystis jiroveci 4) Histoplasma 5) Coccidioides 6) Cryptosporidium 7) Toxoplasma gondii 8) Isospora |
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What are come of the many diseases caused by these organisms?
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disseminated miliary disease, pneumonia, meningitis, encephalitis, esophagitis, diarrhea, osteomyelitis, retinitis, vaginitis, and thrush
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What organism is responsible for the classically described pneumonia in AIDS patients?
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P. jiroveci
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What method is commonly used to screen for HIV?
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ELISA
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What test is used to confirm the diagnosis if an ELISA test is positive for HIV?
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Western blot for p24
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What is the most sensitive method for early detection of HIV?
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PCR
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Why else is PCR helpful in managing HIV?
What is the viral load? |
Helps estimate viral load, drug response, and prognosis
The level of replicating virus in plasma determined by PCR |
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What is the significance of the viral load?
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Indicator of the rate of progression to AIDS
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Why is PCR not used to screen for HIV?
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Cost
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What are the three basic categories of antiviral drugs?
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Nucleoside reverse-transcriptase inhibitors
Nonnucleoside reverse transcriptase inhibitors Protease inhibitors |
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What are nucleoside reverse-transcriptase inhibitors (NRTIs)
What are some examples? |
Agents that are phosphorylated by host cell kinases that terminate and/or inhibit reverse transcriptase
Lamivudine Stavudine Zalcitabine Zidovudine Didanosine Abacavir |
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What are nonnucleoside reverse-transcriptase inhibitors (NNRTIs)?
What are some examples? |
Agents that inhibit the action of reverse transcriptase that bind to a site on reverse transcriptase that is different than NRTIs
Delavirdine Efavirenz Nevirapine |
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What are protease inhibitors?
What are some examples? |
Agents that inhibit HIV-1 protease which prevents cleavage of viral precursors
Indinavir Nelfinavir Ritonavir Saquinavir Amprenavir |
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Why are anti-HIV drugs theoretically more effective early in the course of the disease?
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There are fewer mutations and less resistance early in the course of the disease
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