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Displaying record number 59058

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HXB2 Location	Nef(64-74) DNA(8986..9018)	Nef Epitope Map
Author Location	Nef(64-74)
Epitope	EEVGFPVKPQV	Epitope Alignment
		Show epitope variants
Epitope Name	Nef 64-74
Subtype	C
Species (MHC/HLA)	human(B*45:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	CH131: A*23:01, A*29:01, B*15:03, B*45:01, C*02:02, C*06:02
Country	Malawi
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, escape, acute/early infection, optimal epitope

Notes

• 17 patients were examined completely for T cell responses to HIV-1 using epitope entropy and T cell selection pressure. Vertical immunodominance profiles were followed using autologous founder virus and subsequent variant sequence peptides. The time taken for HIV-1 to escape T-responses was primarily related to relative immunodominance (39%) and fitness constraints on epitope variability. Escape was slowed by lower average epitope entropy.
• Escape occurred in all subjects within 70 days from Fiebig I/II (50 days for 15/17 subjects). Rapid escape was restricted by a broad range of HLA, not just protective HLA allotypes. Only 14% of epitopes remained invariant throughout the study, 1,187 days from Fiebig stages I/II. Slower escaping epitopes could be restricted by protective HLA, suggesting that slow escape does not equate to low immune pressure.
• Optimal epitope EEVGFPVKPQV (Nef 64-74) which was part of reactive peptide IEAQEEGEEVGFPVKPQV, elicited an immunodominant response that persisted and reached 50% escape from transmitter/founder sequence at ˜ 30 days from Fiebig Stage I/II. This epitope is restricted by the B*4501 allele which was labeled as non-protective.

References

Liu2013a Michael K. P. Liu, Natalie Hawkins, Adam J. Ritchie, Vitaly V. Ganusov, Victoria Whale, Simon Brackenridge, Hui Li, Jeffrey W. Pavlicek, Fangping Cai, Melissa Rose-Abrahams, Florette Treurnicht, Peter Hraber, Catherine Riou, Clive Gray, Guido Ferrari, Rachel Tanner, Li-Hua Ping, Jeffrey A. Anderson, Ronald Swanstrom, CHAVI Core B, Myron Cohen, Salim S. Abdool Karim, Barton Haynes, Persephone Borrow, Alan S. Perelson, George M. Shaw, Beatrice H. Hahn, Carolyn Williamson, Bette T. Korber, Feng Gao, Steve Self, Andrew McMichael, and Nilu Goonetilleke. Vertical T Cell Immunodominance and Epitope Entropy Determine HIV-1 Escape. J. Clin. Invest., 123(1):380-393, 2 Jan 2013. PubMed ID: 23221345. Show all entries for this paper.

Displaying record number 61079

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HXB2 Location	Nef(64-74) DNA(8986..9018)	Nef Epitope Map
Author Location	Nef(64-74)
Epitope	EEVGFPVKPQV	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	CH131: A*23:01, A*29:01, B*15:03, B*45:01, C*02:02, C*06:02
Country	Malawi
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	computational epitope prediction, escape, acute/early infection, mutation acquisition

Notes

• 17 patients with acute HIV-1 infection were followed to validate that (1) relative escape rate (2) location and identity of escape mutations and (3) epistatic effects on escape, could be predicted within a host by using a simple model based on population genetics and known fitness measures of HIV polyproteins. In general escape location was found most at residues with the lowest fitness cost and escape time correlates with early detection of mutants when T cell response was first detected.
• Epitope EEVGFPVKPQV had a fitness cost ΔE of -0.619 and T cell response was first detected to it at 7d, escape time was 18.9 days.

References

Barton2016 John P. Barton, Nilu Goonetilleke, Thomas C. Butler, Bruce D. Walker, Andrew J. McMichael, and Arup K. Chakraborty. Relative Rate and Location of Intra-Host HIV Evolution to Evade Cellular Immunity Are Predictable. Nat. Commun., 7:11660, 23 May 2016. PubMed ID: 27212475. Show all entries for this paper.