Microbiology - Moffat - HIV Replication and Pathogenesis and Blair - AIDS Flashcards
(23 cards)
What are the two most common routes of infection for HIV?
Unprotected sex
Needle sharing
Who are the most at-risk groups for HIV transmission?
Gay and bisexual men (63%) Heterosexuals (25%) IV drug users (8%) Gay and bisexual men who also inject drugs (3%) **she will ask a question on this
What does HIV having a small Ro mean?
Ro
It means that one exposure is usually not enough to infect a person
For example, a large Ro would be influenza
T/F: Women are more likely than men to become infected.
True
When is PAP most effective?
Hours to days after exposure
What cells does HIV first infect?
Lymphoid cells embedded in the vaginal and rectal epithelium, then spreads to the lymph nodes and blood
T/F: HIV is a diploid RNA virus.
True, but each copy of the virus may be different.
HIV is a ssRNA (+) strand retrovirus
“lentivirus” - slow to cause disease
When do syncitia form?
Late during infection
Depends on the host response if they form or not
New cell tropism
CXCR4 receptor (T cells)
What was the first and is the major target of antiretrovirals?
Reverse transcriptase
Protease is the next big target
Read the HIV lifecycle overview.
- Attachment and fusion
- Uncoating
- Reverse transcription
- Migration of genome to nucleus
- Integration into host chromosome
- mRNA and genome synthesis
- mRNA export
- Viral protein synthesis
- Genomic RNA export
- Spliced mRNA synthesis
- Viral membrane protein synthesis
- Protein maturation
- Protein accumulation at plasma membrane
- Virion assembly at plasma membrane
- Budding
- Virion maturation (immature virions are not yet infectious)
Human susceptibility to HIV infection depends on what protein?
Presence of CCR, chemokine receptor, which can be found on macrophages and T cells. Some people have genetic variants of this that make them less susceptible to HIV infection.
What is the primary obstacle to eradicating HIV from a person?
Latency after the viral genome has incorporated itself into the host genome
Best characterized reservoir = infected resting memory CD4+ T cells, but other reservoirs can include the brain, macrophages, hematopoietic stem cells.
Phase I of HIV replication ends with integration into the host genome. What does Phase 2 consist of?
Lytic replication using host RNA Polymerase II
T/F: Discontinutation of HAART allows viral relapse from latent reservoir.
True
How is the HIV virion made infectious?
The viral protease packaged in the virion must cleave Gag into its three subunits (MA-CA-NC) to form infectious particles. Therefore, protease therapy blocks infectivity of HIV to other cells
What happens in HIV syncytium formation?
HIV infected T cells can fuse with uninfected T cells.
**this is a major cause of immunodeficiency.
Not all strains form syncytia, but those that do are more virulent.
When does HIV become AIDS?
Classified as T cells
What are the possible symptoms of AIDS?
Encephalitis Meningitis Retinitis (ie from CMV) Pneumocystis Pneumonia Tumors (pulmonary, GI, skin) Kaposi Sarcoma (HHV8) Progressive multifocal leukoencephalopathy, PML (brain) Esophagitis, esophageal candidiasis Chronic Diarrhea Oral hairy leukoplakia (tongue) Seborrheic Dermatitis Nodular prurigo Opportunistic infections ie TB (multiple organs), Thrush, toxoplasmosis etc.
T/F: Direct killing of T cells by HIV replication accounts for the immune dysfunction.
FALSE. The immune system seems to take a harder hit than the loss of T cells would suggest.
Activated T cells are even thought to be responsible for releasing cytokines that kill their own kind.
Why are defective HIV virions harmful to the host?
Toxicity
When are HIV antibodies first seen?
Within 3-12 weeks of infection
At what CD4+ and viral load is treatment with HAART recommended.
At any level. However non-adherence is a major obstacle especially to early ART therapy.
Besides RT and protease, what are some other targets of HIV therapy?
Integrase inhibitors
CCR5 and CXCR4 inhibitors (entry level)
Fusion inhibitors