Chapter 13 Part 2 Flashcards
What cells are specialised for type I interferon production early in viral infection?
plasmacytoid DCs
What is the benefit of a segmented genome?
the ability ot reassort during viral replication
What is the fucntion of hemagglutinin on influenza?
repsonseibl for viral binding to and entry into cells
What is antigenic drift?
emergence of point mutations to alter binding sites– can grow in cell immune to previous strain but as T cells and some antibodies can recognise epitopes that have not been altered will only get a mild disease
Waht is antigenic shift?
reassortment of the segmented RNA genomes of 2 different influenza viruses when they are able to infect the same cell reuslting in large changes in their haemagglutinin so T cells and antibodies to previous infections are not protective
What is a neutralising antibody?
prevent the virus from binding and infecting cells
What is dislocation?
when viruses catalyse the degradation of newly synthesised MHC-I molecules by initiating hte pathway normall used to degrade misfoleded ER proteins by directing them back into the cytosol and the ERAD pathway for disposal
How does CMV evade NK cytolysis?
produces a homolog of HLA class I - UL18 which binds LIR-1 on nk cells providing an inhibitory signal
What is the function of cytosolic ICP47 produced by herpes simplex?
prevents peptides from binding to TAP in the cytosol
What is hte function of US6 protein produced by CMV?
interferes with the ATP-dependent transfer of peptides through TAP
What is the function of E19 produced by adenovirus?
competes with tapasin and inhibits peptide loading onto nascent MHC-I molecules
What is the function of mK3 protein produced by murine herpes simplex virus?
directs the addition of ubiquitin subunits with K48 linkages resulting in degradation via proteasome
What cytokine homolog does CMV use to impair antiviral responses?
cmvIL-10 which downregulates pro-inflammatory cytokines
What do herpes viruses express in order to undergo a lysogenic phase?
express the latency associated transcript
What is the function of the latency associated transcript?
suppresses the transcription of the remaining viral genome and produces factors that interfere with host cell apoptosis
How does EBV enter B cells?
using CD21 (CR2) and MHC-II
What is the function of EBNA1 produced by EBV?
interacts with teh proteasome to prevents its own degradation into peptides that would otherwise elicit a T cell repsonse
What are the differences between HIV-1 and HIV-2?
HIV-2 is only really found in West Africa; HIV-1 replicates to higher viral loads in the blood and is more easily transmitted, HIV-2 is rarley vertically transmitted
what is the most common variant of HIV-1?
group M
What makes up the HIV viral spike?
gp120/gp41
What is the function of the RNA transcripts produced from the integrated viral DNA?
mRNAs to direct synthesis of viral proteins and the RNA genomes of new viral particles
What group of viruses does HIV belong to?
lentiviruses
What are the 3 cell targets of HIV?
CD4 T cells; macrophages and DCs
What is cellular tropism?
its ability to enter particular cell types
What determines HIV’s cellular tropism?
expression of specific receptors fro the virus on the surface of those cells
What are the major coreceptors for gp120 fusion and entry?
CCR5 and CXCR4
Which cells predominantly express CCR5?
subsets of effector memory CD4 T cells; DCs and macropahges
Which cells predominantly express CXCR4?
naive and central memory CD4 T cells
What happens when gp120 binds CD4?
undergoes a conformational change that exposes a high-affinity site that is bound by the coreceptor
What does binding of the coreceptor to gp120 cause?
gp41 unfolds and inserts a portion of its structure (fusion peptide) inot the plasma membrane of hte target cell
What is found in the viral nucleocaspid?
viral genome and associated viral proteins
How many genes does HIV have?
9
What is the form of DNA produced by reverse transcriptase?
cDNA
What is used by integrase to integrate the cDNA into host DNA?
LTRs that reside at each end of the viral genome
What is the integrated cDNA copy known as?
provirus
What is the function of the gag gene?
encodes structural proteins of the viral nucleocapsid core
What is the function of pol?
encodes enzymes involved in viral replication
What is the function of env gene?
encodes viral envelope glycoprotein
What 3 enzymes does pol encode?
reverse transcriptase; integrase; viral protease
How are gag and pol translated?
as long polypeptide chains that are then cleaved by pol
What is the product of the env gene?
gp160
What is gp160 cleaved into?
gp120 and gp41
What initiates transcription of hte provirus following integration?
host transcription factors which are induced during activation
What is the function of Tat?
enhances transcription from hte provirus and binds to the RNA transcripts, stabilising them in a form that can be translated
What is the function of Rev?
binds to singly spliced or unspliced transcripts and transports them to the cytosol
What si the long-lived latency of HIV related to?
it is a consequence of the toprism of the virus for CD4 T cells
What is the function of vif?
affects particle infectivity
What is the function of viral protein R?
transport of DNA to nucleus, augments virion production, cell cycle arrest
What is the function of viral protein U?
promotes intracellular degradation of CD4 and enhances release of virus from cell membrane
What is the function of nef?
augments viral replication in vivo and in vitro. decreases Cd4, MHC-I and II expression
What 2 transcription factors can initiate transcription of the viral genome?
NFkB and NFAT
How may activation of NFkB take place independetly of antigen?
activation of effector-memory T cells can occur by cytokines
How does Tat work?
binds to a transcriptional activation region in the LTR which recruits cellular cyclin T1 and its partner, CDK9 to form a complex which phosphoryaltes RNA polymerase and enchanes its ability to generate full-length transcripts of the vrial genome
How does Rev work?
binds to Rev response element- a specific viral RNA sequences to prevent degradation of incompletely spliced mRNA transcripts by the host
How does Nef augment viral replication?
lowers the threshold for TCR signalling and downregulates CTLA-4 which results in greater and more sustained T cell activation that promotes viral replication
How does Vif work?
acts to overcome a cytidine deaminase called APOBEC which catalyzes the conversion od deoxycytidine to deoxyuridine in reverse transcribed viral cDNA thereby destroying its ability to encode protein
How does Vpu work?
required to overcome tetherin which inserts into both the plasma membrane of the host cell and the envelope of hte mature virion to block its release
How does Vpr work?
target restriction factor SAMHD1, which limits the intracellular pool of deoxynucleotides available for viral cDNA synthesis
In what forms can the virus be transmitted?
free infectious particles or via infected cells for which the virus has tropism
Why does inital viral replication favoured in Th1 and Th17 cells?
they express CCR5- naive T cells and Th2 don’t
What strains of virus are typically required for transmission and why?
CCR5-tropic R5 strains as CCR5 dominates on CD4-expressing immune cells resident at the major sites of viral transmission;epithelial cells of the rectum and endocervix express CCR5 so R5 can translocate
How can HIV bind to DCs?
binding of viral gp120 to CTLRs eg langerin; mannse receptor and DC SIGN– allows HIV to travel to lymph nodes
Where do the highest number of CD4 T cells in the body reside?
GALT
How may the depletion of immune cells in the gut coumpound rapid production of virus in the GALT?
result in barrier breakdown and translocation of constituents of the microbiota which increases immune cell activation
What is the viral set point?
level of virus that persists in the blood plasma after development of CTL response and antibody production which occurs during the acute phase to control high viraemia
What is the viral set point indicative of?
future disease progression
What does the strong selectie pressure of hte antiviral immune response result in?
selection for HIV escape mutants that are no longer detected by the adaptive immune cells- many viral variants
What happens to the dominanat viral type?
in about 50% it swithces from R5 to X4 variants which results in progression to AIDs
What are the overall functions of the R5 and X4 variants?
R5 variants are critical for HIV transmission whereas X4 variants that emerge under selective pressure contribute to disease progression
What is the correlation between the strength of CD4 T cell proliferative responses to HIV antigen and viral load?
inverse
What are the 2 important aspects of hte antibody resposne to HIV?
generating neutralising antibody against gp120 and gp41 in order to block viral attachment or entry; generating nonneutralising antibodies that target infected cells for ADCC
What are broadly neutralising antibodies?
antibodies able to block infection by multiple viral strains
Why is homozygosity of HLA class I alleles associated with more rapid disease progression?
T cell response to infection is less diverse
Give examples of HLA class I alleles associated with greater prognosis?
HLA-B57; HLA-b27; HLA-B13- delay HIV-1 escape
Why do ARTs not prevent the release of virus?
cells that are already infected as provirus is already established so reverse transcriptase and integrase aren’t needed and inhibition of protease does not stop virus being released
What causes the increase in cD4 T cells with HAART?
redistribution of CD4 T memory cells from lymphoid tissues into circulation as viral replication is controlled; reduction in immune activation so reduces killing of infected CD4 T cells by CD8 cells; emergence of naive T cells from the thymuc
What is the function of APOBEC?>
causes extensive mutation of newly formed HIV cDNA to destroy its coding and replicative capacity
What are quasi-species?
variants of HIV that develop from a single foudner virus
Which viruses share the formation of quasi-species?
all lentiviruses
which HIV gene is respondible for inhibiting the restriction factor SAMHD1?
Vpr
