Viruses Flashcards
What are the differences between plasmacytoid and myeloid dendritic cells, and how do they confer antiviral resistance?
plasmacytoid dendritic cells (pDC)
- Specialized in producing large amounts of type I interferons (IFN-α and IFN-β) in response to viral infections through Toll-like receptor (TLR) signaling.
- limited antigen presentation
myeloid dendritic cells (mDC)
- Efficient in antigen uptake, processing, and presentation to T cells, promoting adaptive immune responses.
- Produce proinflammatory cytokines and chemokines upon activation through various stimuli, including pathogens and inflammatory signals
How are viral antigens processed and presented?
Protein Degradation:
- Proteasomal Degradation: Proteins, including viral antigens, are degraded by the proteasome in the cytoplasm into smaller peptide fragments.
- Endosomal Degradation: Some viral proteins may also be processed by lysosomal proteases following endocytosis and fusion with lysosomes.
Peptide Loading onto MHC Molecules:
- MHC Class I Pathway: Cytosolic peptides generated by proteasomal degradation are transported into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP).
- Peptide Loading: In the ER, peptides bind to newly synthesized MHC class I molecules, which are then transported to the cell surface for presentation to CD8+ T cells (cytotoxic T lymphocytes, CTLs).
T Cell Recognition and Activation:
- CD8+ T Cell Activation: MHC class I-peptide complexes on infected cells are recognized by CD8+ T cells (CTLs), leading to T cell receptor (TCR) engagement, co-stimulation, and activation of CTLs.
What role do CD4 T cells play in antiviral immunity?
- provide help to CD8 T cells (induce proliferation)
- recruit proinflammatory macrophages
- eliminate infected cells
- provide help to B cells to produce antibodies
How do CD8 T cells tackle infection?
- killing cells through release of perforin and granzymes
- trigger death by Fas binding to FasL on infected cell
- produce soluble factor which cure the cell eg IFN-gamma, TNF-alpha
What role do antibodies play in antiviral immunity?
- opsonisation
- prevent binding to receptors
- prevent endocytosis
- prevent fusion
- activate complement
–> destroy virus and opsonisation
–> destroy virus-infected cells
What is the structure of a coronavirus?
- positive, single stranded RNA genome
- enveloped
- zoonotic viruses
- spherical
- cell entry via various receptors
What is the genome structure of SARS-CoV2?
- read in two large ORFs
- proteases cut large polyproteins into 16 smaller proteins
- 2 are proteases responsible for cleavages that make entry into cells much more efficient
What is unique about the polymerase in SARS-CoV2?
RNA viruses tend to be small as RNA is unstable, which is why they mutate so fast
but cov2 has polymerase w proof-reading activity
What are the receptors necessary for HIV entry?
CXCR4 on T cells
CCR5 on macrophages
these allow fusion of lipid envelope w cell membranes facilitating entry into the cell
antiCXCR4 and antiCCR5 can inhibit viral entry
Why are nucleoside/nucleotide analogues effective at inhibiting viruses?
take advantage of the fact that viral polymerases are not as discriminating as cellular polymerases
but are relatively toxic to humans, can cause mutations, and are potentially carcinogenic
How are non-nucleoside reverse transcriptase inhibitors useful?
rather than binding to the active site of HIV RT, they inactivate by binding elsewhere
However, mutations in RT can allow mutants to escape effects
Why is HIV maturation crucial?
- only mature HIV protease is infectious
- driven by virion protease
this protease is a major antiviral target
eg
- natural substrate for HIV-1 protease is 7 amino acids long
–> Saquinivar (Ro 31-8959) mimics this structure
–> fits into active site and doesnt leave, inactivating the enzyme
What is HAART?
Highly Active Anti-Retroviral Therapy
Uses more than one anti-HIV drug
reduces probability of virus acquiring drug resistant mutation
can dampen down replication of HIV to undetectable levels, so patient can live a normal life
v large drug burden however
What is PrEP?
Pre-Exposure Propylaxis
aimed at HIV-negative individuals who are at a substantial risk
contains two drugs - NRTIs
when taken daily, shown to reduce the risk of HIV infection up to 92%
How do anti-herpesvirus drugs work?
nucleoside analogues
- DNA chain terminating
- activated in infected cells by viral Thymidine Kinase
