Host Genetics In Virus Infections Flashcards
What is a major co receptor in HIV entry?
CCR5
What co-receptors are used in HIV entry?
CCR5 and CXCR4
In 1% of Caucasians both chromosomes carry defective delta32-CCR5. What is unique about these individuals?
They are very resistant to HIV1 infection.
Describe delta32/delta32 CCR5 individuals.
Homozygous for this CCR5 mutation are very resistant to HIV1 infection. It is found on 1% of Caucasians and is absent in Africans. There are few reported cases of HIV infection. It is likely that these are due to injection with a non-R5 isolate.
Describe delta32 CCR5 allele heterozygotes.
They have a delayed onset of AIDS and some resistance to infection. It is found in 12-18% of Caucasians, 2% of African Americans. It is absent from Africa.
What effect does the CCR5P polymorphism have?
It accelerates AIDS.
What effect does the CCR2 64I polymorphism have?
It delays AIDS.
What effect does the SDF1 3’A polymorphism have?
It delays AIDS.
What might be a potential cure for HIV?
CCR5 delta32/delta32 stem cell transplantation.
Allers et al. In 2011 found that these individuals remained RNA and cDNA negative at 40 months post transplant.
Researchers are currently exploring transplant with autologous stem cells with engineered CCR5 KO (CROI).
What HLA subtypes were found in HIV-1-exposed seronegative sex workers?
HLA-A*6802 and HLA-B18 associated with cytotoxic T-cell responses to HIV1.
What does HIV progression rate depend on?
Progression rate depends on the viral load set point. The viral loads set point stabilises after a period of acute HIV infection. The set point is reached after the immune system has developed specific cytotoxic T cells and begins to fight the virus.
The higher the viral load at the set point, the faster the virus will progress to AIDS.
The lower the viral load at the set point, the longer the patient will remain in clinical latency.
The only effective way to lower the set point is through highly active antiretroviral therapy.
What are HIV Long-Term Non-Progressors?
They have a stable CD4 count for more than 10 years and no disease symptoms. They account for around 5% of HIV infected individuals.
What are HIV elite controllers?
Elite controllers are HIV infected individuals who are not taking ARVs who maintain undetectable loads of less than 50 copies per ml. 1 in 300 patients are elite controllers.
What are viremic controllers?
Viremic HIV controllers are infected individuals not taking ARVs whose viral load is less than 2000 copies per ml of blood.
Why are some HLAs protective against HIV and others not?
Some alleles can allow virus escape due to point mutations in key residues associated with HLA binding.
Some mutations are neutral.
Some alleles induce a fitness cost leading to immune driven-attenuation akin to ARV resistance mutations. Need compensatory mutations.
