Retrovirus Flashcards
Generally what are retroviruses?
Enveloped RNA viruses that contain reverse transcriptase, producing a DNA provirus that integrates into host genomes
Mainly bloodborne transmission
What membrane proteins do HIV viruses have?
Glycoproteins 41 and 120
What cell does HIV bind to?
CD4 helper T cells
What cells initiate HIV infection?
Dendritic cells, bringing HIV from mucosal surfaces to lymphoid tissue where they infect CD4 T cells
Describe the stages in HIV infection
1) Virus binds to CD4 lymphocyte via gp120 binding to receptors
2) Virus enters the cell
3) Reverse transcriptase transcribes viral RNA to DNA
4) Viral DNA enters the nucleus and integrates into host genome
5) T-cell activation in future induces low level transcription of the provirus
6) RNA transcripts are spliced, allowing for translation of early genes
7) Early genes code for proteins amplifying viral RNA transcription and transport RNA to the cytoplasm
8) Viral RNA and proteins are packaged into virus particles, budding from the cell to spread
Classes of antivirals against HIV
NRTI - nucleoside reverse transcriptase inhibitor
NNRTI - non-nucleoside reverse transcriptase inhibitor
PI - protease inhibitor, blocking action of proteases cleaving HIV polypeptides
INSTI - integrase strand transfer inhibitor, preventing integration of provirus into host genome
Not as impt:
Fusion inhibitor - competitively binds to gp41, blocking fusion of HIV to CD4
Entry inhibitor - binds to CD4 T cell surface proteins to prevent HIV binding
Pathogenesis of HIV infection
Lytic infection of CD4 T cells, causing lysis to release viral particles
Latent infection of CD4 T cells, integrating into host genome with low levels of replication
Persistent infection of macrophages, dendritic cells and monocytes
Disrupts neuronal function
Initially after exposure there are flulike symptoms (acute febrile illness)
Long clinical latency, about 10 years
Eventually overwhelms cell immunity, causing high viral loads and causing immunodeficiency due to progressive loss of CD4 T cells, reducing B cell control and allowing for severe systemic opportunistic infections (AIDS)
What is the function of CD4 T cells?
CD4 T cells play critical roles in activating and regulating cell-mediated immune responses, especially towards extracellular pathogens
How is HIV transmitted?
Blood, semen, vaginal secretions
Can transmit during latency period!
Injecting drug users, hemophiliacs, tattoos, healthcare workers, sexual intercourse, peripartum transmission
Can HIV spread through saliva?
Low possibility
HIV cannot survive in cell-free state in saliva due to presence of IgA group antibodies
High molecular weight mucins entrap the virus
Salivary leucocytes protease inhibitor (SLPI) blocks cell surface receptors needed for HIV entry into cells
How to kill HIV virus?
Heat
Glutaraldehyde, hypochlorite
AIDS-defining illnesses?
Lots of stuff including candida infection, chronic mucocutaneous herpes simplex, herpes zoster, oral hairy leukoplakia (EBV), Kaposi sarcoma (HHV8 causing tumours from endothelial cells of blood vessels)
HIV diagnosis
Initial screening via HIV antibody or HIV antigen-antibody combination tests
Western blot analysis rules out false positives
RNA PCR
Exposed persons should be tested again 4-6 weeks later to rule out false negatives
AIDS diagnosis
1) Positive for the virus
2) Either have low CD4 count (<200/ul), or experience one or more of the AIDS defining illnesses
Prevention and Treatment of HIV
No vaccine so dont be promiscuous and use condoms
Therapies slow down disease progress or diminish symptoms
- Inhibit viral enzymes
- Inhibit fusion
- Inhibit viral integration
- Highly active anti-retroviral therapy (HAART)
