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Displaying record number 53634

HXB2 Location  Pol(283-290)   Pol Epitope Map
View variants at this location
Epitope TAFTIPSI   Epitope Alignment
Variants
TAFTIPSt   diminished response; susceptible form
TAFTIPSm   diminished response; susceptible form
Species (MHC/HLA human(B51)

Variant Details

Showing all: 2 variant(s).


Variant ID.  118
Epitope Seq.  TAFTIPSI
Variant Seq.  TAFTIPSt
Mutations I/T
Epitope Location I8T
HXB2 Location I290T
Mutation Type DR: diminished response
SF: susceptible form
Method Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Note Prior to the initiation of therapy, taftipsT variant was found in 24/24 clones. At week 14 of therapy, this variant was completely replaced with taftipsI. By week 19, a complete replacement occurred again, this time to taftipsM. The change at nucleotide level suggests a stepwise progression from ACA to ATA to ATG. The taftipsT and taftipsM variants had lower avidity than the taftipsI variant, but this wasn't evident at saturating conditions; only careful titrations revealed the difference. HLA-B51 stabilization studies revealed the increased stabilization with the taftipsI form. Also, CD3 down-regulation was larger in response to taftipsI. The viral shift to the taftipsM variant during HAART was predicted to have minimal or undetectable effect on drug sensitivity.


Variant ID.  119
Epitope Seq.  TAFTIPSI
Variant Seq.  TAFTIPSm
Mutations I/M
Epitope Location I8M
HXB2 Location I290M
Mutation Type DR: diminished response
SF: susceptible form
Method Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Note Prior to the initiation of therapy, taftipsT variant was found in 24/24 clones. At week 14 of therapy, this variant was completely replaced with taftipsI. By week 19, a complete replacement occurred again, this time to taftipsM. The change at nucleotide level suggests a stepwise progression from ACA to ATA to ATG. The taftipsT and taftipsM variants had lower avidity than the taftipsI variant, but this wasn't evident at saturating conditions; only careful titrations revealed the difference. HLA-B51 stabilization studies revealed the increased stabilization with the taftipsI form. Also, CD3 down-regulation was larger in response to taftipsI. The viral shift to the taftipsM variant during HAART was predicted to have minimal or undetectable effect on drug sensitivity.

References

Casazza2005a Joseph P. Casazza, Michael R. Betts, Brenna J. Hill, Jason M. Brenchley, David A. Price, Daniel C. Douek, and Richard A. Koup. Immunologic Pressure within Class I-Restricted Cognate Human Immunodeficiency Virus Epitopes during Highly Active Antiretroviral Therapy. J. Virol., 79(6):3653-3663, Mar 2005. PubMed ID: 15731259. Show all entries for this paper.


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