Human Immunodeficiency Virus Pathogenesis Flashcards
What are the three phases of HIV infection?
initial acute phase
variable asymptomatic phase
end-stage disease
What is the clinical difference between HIV1 and HIV2?
HIV2 also progresses to AIDS
but usually longer incubation period, and lower morbidity
How is HIV1 sub-divided further in classification?
Groups
M (major) 95% of all cases
N (new)
O (outlier)
P
Clade -
Group M subtyped into different clades
A, B, C, D, F, G, H, J, K
Different prevalence in different geographic areas
Groups N, O, P do not have clades
What proteins does HIV genome code for?
Gag
Pol
Env
Auxillary proteins - essential for viral reproduction
Tat
Rev
Additional proteins - help modify reproduction
Nef
Vif
Vpr
Vpu
Additional proteins
What is the role of Vif protein?
Vif - viral infectivity factor
disrupts anti-viral activity of CD4 cells
Additional proteins
What is the role of Vpr protein?
Vpr - viral rapidity protein
helps transport HIV genome into nucleus of CD4 cell
Additional proteins
What is the role of Vpu protein?
Vpu -
enhances release of virions from plasma membrane of infected cells
Additional proteins
What is the role of Nef protein?
Nef - negative factor
downregulates MHC-1 presentation from infected cells - preventing infected CD4 cells from being killed
Following HIV infection, antibodies are produced.
Why can they not stop further infection progression?
Antibodies can be produced which are neutralising - preventing virus entering CD4 cells
However, over time, virus can mutate to evade these antibodies
Also antibody production decreases as CD4 cells die due to HIV infection
Infected person may release 100 000 000 000 new virions into blood per day. Overwhelm antibody response
Additionally, virus coated in antibodies can actually facilitate entry into susceptible cells - enhancing antibodies.
How does HIV enter the CNS?
Infected monocytes/ CD4 T cells enter by transcytosis across BBB
They then infect microglial cells which form multinucleated giant cells
What is HIV role in cancer?
40% of untreated HIV patients will develop malignancy
HIV does not promote oncogenesis. But it reduces the immune systems ability to control proliferation of abnormal cells - e.g Kapsoi sarcoma, B cell lymphoma
Patients with HIV are at risk of HHV8 disease
What clinical pictures is this associated with?
Kaposi sarcoma
B-cell lymphoma
The Berlin patient was “cured” of HIV
What mutation did the bone marrow donor have?
CXR5 delta 32 mutation
confers resistance to HIV
