B9: HIV Flashcards
What is HIV and what syndrome does it cause?
HIV is a lentivirus that infects humans and causes Acquired Immune Deficiency Syndrome (AIDS).
When was AIDS first described and where was HIV thought to be present earlier?
AIDS was first described in 1981, although HIV is thought to have been present in Africa on a smaller scale since the 1930s.
What is the difference between HIV-1 and HIV-2?
: HIV-1 is responsible for the majority of AIDS cases worldwide, while HIV-2 is less pathogenic and primarily found in West Africa.
What early cases and groups were involved in the initial identification of AIDS (timeline beginning)?
In 1978, signs were seen in gay men in the US and Sweden, and heterosexuals in Tanzania and Haiti began showing symptoms that would later be called AIDS.
What significant events in the timeline of AIDS occurred in 1981–1984
981: At least 26 cases (including biopsy-confirmed Pneumocystis carinii pneumonia in young gay men) in the US.
1982: The CDC links the disease to blood, and the term AIDS is first used.
1983: Luc Montagnier and Françoise Barré-Sinoussi discover HIV at the Institut Pasteur.
1984: Dr. Robert Gallo also “discovers” the virus.
What type of virus is HIV-1 in terms of its genome?
HIV-1 is a complex retrovirus with a positive-sense RNA genome that is reverse transcribed into DNA.
Which core retroviral genes does HIV-1 contain?
gag, pol, and env.
: What are the six accessory genes encoded by HIV-1?
The accessory genes are vif, vpr, tat, rev, vpu, and nef.
What does the gag gene encode?
It encodes the group-specific antigen proteins that form the capsid and core structural components.
What does the pol gene encode?
enzymes essential for viral replication, including reverse transcriptase (RT), integrase (IN), and protease (PR).
What is the function of the env gene?
encodes the envelope glycoproteins (gp120 and gp41) responsible for binding and fusion with host cells.
How does HIV-1 initially bind to its target cell?
The surface glycoprotein gp120 binds with high affinity to the CD4 receptor on CD4⁺ lymphocytes and monocyte/macrophage lineage cells.
What happens after gp120 binds to CD4?
gp120 undergoes a conformational change that exposes a binding site for a co-receptor (either CCR5 or CXCR4).
How do co-receptors influence HIV tropism?
Viruses that bind CCR5 are macrophage tropic, while those that use CXCR4 are T-cell tropic.
What role does gp41 play during HIV entry?
After co-receptor binding, gp41 mediates the fusion of the viral and cellular membranes, allowing the virion core to enter the cell.
Describe HIV viral uncoating and transport to the nucleus.
The capsid remains intact as it is transported via the microtubule network; viral proteins with nuclear localization sequences (NLS) help transport the pre-integration complex (PIC) through the nuclear pore.
What unique ability do lentiviruses like HIV have regarding the cell cycle?
They can infect non-dividing cells because the intact capsid (and associated PIC) can traverse the nuclear pore.
How is HIV DNA integrated into the host genome?
The pre-integration complex (PIC) is imported into the nucleus, and viral integrase modifies the cDNA ends and integrates the provirus into host chromatin, preferably in transcriptionally active euchromatin.
What role does the provirus play in HIV replication?
The integrated proviral DNA acts as a template for the production of viral mRNAs and new genomic RNA using the host’s RNA polymerase II.
What are the key features of the HIV long terminal repeats (LTRs)?
The 5’ LTR contains a TATA-box and binding sites for transcription factors (e.g., NFAT, NF-κB, Sp1), and the LTRs regulate transcription initiation and termination.
How does the viral protein Tat enhance HIV transcription?
Tat binds to the TAR element on nascent RNA and recruits Cyclin T/CDK9, which phosphorylates the CTD of RNA polymerase II, promoting transcription elongation.
What are the different types of HIV mRNAs produced?
mRNAs can be unspliced (genome and gag-pol), singly spliced (env/vpu, vif, vpr), or doubly spliced (tat, nef, rev).
What is the role of the HIV protein Rev in mRNA transport?
: Rev, produced from doubly spliced mRNA, shuttles back to the nucleus, binds to the Rev Responsive Element (RRE) on unspliced and singly spliced mRNAs, and facilitates their export to the cytoplasm for translation.
How are the HIV structural proteins synthesized and assembled?
Gag and gag-pol polyproteins are expressed in the cytosol; they assemble into the capsid, and final maturation occurs after budding through proteolytic cleavage.
What cellular machinery assists HIV virion budding?
The ESCRT (Endosomal Sorting Complex Required for Transport) system is used to facilitate budding and release.
How does the HIV accessory protein Vif function?
Vif targets the antiviral enzyme APOBEC3G for degradation by binding it to a Cullin5 ubiquitin ligase complex, preventing hypermutation of the viral genome.
What functions does the HIV protein Nef serve?
Nef downregulates cell surface CD4 and MHC I, reducing superinfection and protecting infected cells from cytotoxic T cells, and also aids in budding via interactions with ESCRT machinery.
Describe the role of Vpu in HIV replication.
Vpu enhances virion release by counteracting the host protein tetherin (BST-2), which normally traps budding virions, and it also targets intracellular CD4 for degradation.
What roles does Vpr play in HIV replication?
Vpr interacts with Gag during packaging, aids in the nuclear import of cDNA, induces G2/M cell cycle arrest, and promotes transcription from the HIV LTR.
What characterizes the acute phase of HIV infection?
Acute infection is marked by high viral loads, a rapid decline in CD4⁺ T cells (especially in the intestine), and flu-like symptoms.
What defines the clinical latency phase of HIV infection?
Clinical latency is a prolonged asymptomatic phase where viral replication continues in lymphoid tissues at a stable “set point” that predicts progression.
How is AIDS clinically defined?
AIDS is defined by a CD4⁺ T cell count of less than 200 cells/μl and high viral loads, leading to vulnerability to opportunistic infections.
What are some common AIDS-defining illnesses?
Examples include candidiasis, cryptococcosis, tuberculosis, Mycobacterium avium complex (MAC), Pneumocystis pneumonia (PCP), and wasting syndrome.
What are the main classes of antiretroviral drugs used to treat HIV?
They include nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, fusion inhibitors, and CCR5 antagonists.
What is the concept behind Highly Active Antiretroviral Therapy (HAART)?
HAART (or ARV therapy) uses a combination of three or more drugs targeting different steps of the HIV lifecycle, reducing the chance of resistance and effectively controlling viral replication.
