How Viruses Cause Disease - HIV Flashcards
EPIDEMIOLOGY
I) how many people were living with HIV in 2020? What % of people living with HIV know their status?
Ii) is the number of new diagnoses of HIV in the UK increasing or decreasing?
Iii) are more men or women diagnosed in the UK?
Iv) what is the most common age group at diagnosis?
I) 37.7 million people are living with HIV globally in 2020 - 84% of people know their status Ii) new diagnoses are decreasing Iii) men Iv) 35-49yrs
HIV VIROLOGY
I) what type of virus is it? What are the two main types?
Ii) which type is less pathogenic/transmissible?
Iii) which area of the world has the highest HIV1 genetic diversity?
Iv) name two membrane proteins found on HIV1? What type of RNA is found inside?
I) retrovirus - HIV1 and HIV2 Ii) HIV 2 is less pathogenic Iii) west central Africa Iv) gp120 and gp41 - 2 identical molecules of ssRNA are found inside
HIV TRANSMISSION
I) name three ways it can be passed on
Ii) name two things that increase risk of transmission
Iii) what route has the highest risk of transmission?
I) blood exchange (parenteral), sexual contact (sexual exposure), mother to child (vertical)
Ii) other STIs (inc number of target cells) and high HIV viral load
Iii) blood transfusion has highest risk of transmission
HIV PATHOGENESIS
I) CD4 T cells in which location are rapidly depleted early on in untreated HIV infection? Where are they also lost from?
Ii) name three things that are dramatically increased in acute response to HIV infection
Iii) what happens to levels of HIV RNA after antiretroviral therapy? Which CD4 cells show reduced recovery?
Iv) what happens to HIV specific T cells after anti retro viral therapy? Do antibodies persist?
I) rapid depletion of GI tract CD4 cells, but also lost from the blood
Ii) acute infection - markers of immune activation and prod do non neutralising antibodies and HIV specific CD4 and CD8 cells are increased
Iii) HIV RNA decreases post antitretroviral therapy but GI tract CD4 cells show reduced recovery
Iv) HIV spec T cells reduce after anti retro viral therapy but antibodies persist
HIV RESERVOIR
I) where does latent infection reside? How is this maintained?
Ii) why can’t current antiretroviral treatment eradicate the infection? (2)
Iii) what may happen if ART is discontinued?
I) latent infection in memory CD4+ T cells - maintained indefinitely through homeostatic proliferation
Ii) current ART can’t elim the infection as it can’t eliminate integrated viral DNA from the infected cells and residual replication still occurs in the HIV reservoir
Iii) discont ART - HIV reservoir allows increased replication and emergence of the virus
HOST RESPONSE AND PATHOGENESIS
I) which type of cells mediate HIV decline after acute infection? What branch of the immune system does this involve? What happens to these cells over time?
Ii) name two ways HIV evades the immune system
Iii) depletion of which cells leads to development of opportunistic infections and AIDS related malignancies?
Iv) name three things that happen when there is activation of the endothelium and coagulation system due to a constant state of immune activation?
I) HIV specific CD8 cytotoxic T lymphocytes - adaptive immune system but over time fails to control the virus
Ii) immune evasion by increasing glycosylation of the envelope as a shielding mechanism and evasion from cellular restriction factors eg APOBEC3
Iii) depletion of circulating and tissue based CD4 T cells
Iv) increased pro inflam cytokines (IFN, IL6, TGFb). Serum markers of sinflam (CRP, cystatin and D Dimer), low CD4:CD8 ratio and exhaustion/senescence of T cells and monocytes
PATHOGENESIS OF HIV INFECTION
I) what do changes to intestinal lymphoid tissues lead to?
Ii) circulation of which molecule enhances persistent immune activation?
Iii) name three things seen due to the sustained inflammatory state
Iv) which cells in the CNS can be infected with HIV? Which cells in the kidneys can be infected? Name the conditions that these infections form the basis for
I) marked increase in microbial translocation due to disruption of the physiol gut barrier
Ii) circ of LPS (bac cell wall component) enhances immune activation via toll like receptors
Iii) premature ageing, multi organ disease, osteoporosis
Iv) HIV infects astrocytes in CNS > HIV assoc neurocog disorder
HIV infects renal epithelial cells > HIV assoc nephropathy
PRIMARY HIV INFECTION
I) what % of patients have symptoms?
Ii) what are the two things that characterise it?
Iii) name four differentials for primary HIV1 infection
Iv) what staging system is used to determine days follow transmission? What is the eclipse stage?
V) what stage is the asymptomatic stafe? What is viral load predictive of in this stage?
I) 50-90% patients have symptoms
Ii) characterised by high viral load and high risk of transmission
Iii) differentials - EBV, CMV, primary HSV, streptocococcal disease, Lyme disease, SLE
Iv) use fiebig stages
- eclipse - no markers found in the plasma - initial replication of virus at inoculation site and spread to satellite lymphoid organs
V) fiebig stafe VI = asymptomatic
- high viral load in this stage is predictive of rate of disease progression/CD4 count decline
AIDS STAGE
I) what is the CD4 count defined as?
Ii) name four opportunistic infections that may occur in this phase
Iii) name three AIDS related malignancies
I) CD4 count <200 cells/mm3
Ii) Candida of bronchi, trachea, lungs/CMV, encephalopathy, mycobacterium TB, PCP pneumonia, salmonella septaecaemia
Iii) cervical cancer, kaposi sarcoma, Burkitts lymphoma, immunoblastic lymphoma
VIRAL PATHOGENESIS
I) name three things essential for viruses to infect a host
Ii) can viruses replicate outside of permissive host cells?
Iii) name a host cell receptor recognised by HIV and one by rhinoviruses - what does binding to these receptors permit?
Iv) name a pro viral factor that hep C virus interacts with on host hepatocytes
V) name a host restriction factor that can be inhibited by a virus which allows it replicate and cause disease
I) virus must overcome natural barrier to infection (skin and mucosa), primary replication at initial site of infection and movement to secondary replication sites
Ii) no
Iii) HIV recog CCR5/CXCR4 and rhinovirses recog CD54
Iv) hep C interacts with miR-122 specifically expressed on hepatocytes
V) host restriction factor - host proteins that inhibit ability of virus to replicate = APOBEC
PATHOGENESIS OF VIRAL INFECTIONS
I) what is rapidly activated in the innate immune response in relation to viral infection
Ii) name a cell that is part of the adaptive immune system that clears the virus and gives long term immunity
Iii) name three direct cytoplasmic effects that are caused by the virus replicating in the host cell
Iv) do viruses cause direct or indirect immune mediated cell death?
V) name a virus that leads to dev of immune complexes (aggregates of virus and ABs that ppt in blood vessels and cause inflam)
Vi) name three ways in which viruses can promote the onset of cancer
I) type I interferon system
Ii) CD8 T cells
Iii) inhib of cell transcrip/translation, changes in membrane permeability, alt of cytoskeleton, cell cell fusion, induc of apoptosis
Iv) indirect
V) Hep C
Vi) via immunosuppression (HIV and kaposi), chronic inflam (HCV and HCC) and cellular transformation (HPV and cervical cancer)
SUMMARY
I) what is causing the incidence of HIV to decline globally and in the UK?
Ii) name the two things that mediate HIV pathogenesis
I) anti retro viral tx and prevention measures eg PrEP
Ii) immunosupression (loss of CD4 cells) and chronic inflam
