PMID- 31048489
OWN - NLM
STAT- MEDLINE
DCOM- 20191031
LR  - 20191116
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 364
IP  - 6439
DP  - 2019 May 3
TI  - Structural topology defines protective CD8(+) T cell epitopes in the HIV 
      proteome.
PG  - 480-484
LID - 10.1126/science.aav5095 [doi]
AB  - Mutationally constrained epitopes of variable pathogens represent promising 
      targets for vaccine design but are not reliably identified by sequence 
      conservation. In this study, we employed structure-based network analysis, which 
      applies network theory to HIV protein structure data to quantitate the 
      topological importance of individual amino acid residues. Mutation of residues at 
      important network positions disproportionately impaired viral replication and 
      occurred with high frequency in epitopes presented by protective human leukocyte 
      antigen (HLA) class I alleles. Moreover, CD8(+) T cell targeting of highly 
      networked epitopes distinguished individuals who naturally control HIV, even in 
      the absence of protective HLA alleles. This approach thereby provides a 
      mechanistic basis for immune control and a means to identify CD8(+) T cell 
      epitopes of topological importance for rational immunogen design, including a T 
      cell-based HIV vaccine.
CI  - Copyright (c) 2019 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Gaiha, Gaurav D
AU  - Gaiha GD
AUID- ORCID: 0000-0001-6875-4472
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
AD  - Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
FAU - Rossin, Elizabeth J
AU  - Rossin EJ
AUID- ORCID: 0000-0002-0052-9575
AD  - The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
AD  - Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA.
FAU - Urbach, Jonathan
AU  - Urbach J
AUID- ORCID: 0000-0003-0597-2848
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Landeros, Christian
AU  - Landeros C
AUID- ORCID: 0000-0002-6529-253X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Collins, David R
AU  - Collins DR
AUID- ORCID: 0000-0001-7903-346X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
FAU - Nwonu, Chioma
AU  - Nwonu C
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Muzhingi, Itai
AU  - Muzhingi I
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Anahtar, Melis N
AU  - Anahtar MN
AUID- ORCID: 0000-0003-0309-368X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
AD  - Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
FAU - Waring, Olivia M
AU  - Waring OM
AUID- ORCID: 0000-0001-9261-0516
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
AD  - Institute for Medical Engineering and Science, Massachusetts Institute of 
      Technology, Cambridge, MA 02139, USA.
FAU - Piechocka-Trocha, Alicja
AU  - Piechocka-Trocha A
AUID- ORCID: 0000-0002-1547-524X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
FAU - Waring, Michael
AU  - Waring M
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
FAU - Worrall, Daniel P
AU  - Worrall DP
AUID- ORCID: 0000-0002-7760-9848
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Ghebremichael, Musie S
AU  - Ghebremichael MS
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Newman, Ruchi M
AU  - Newman RM
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Power, Karen A
AU  - Power KA
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Allen, Todd M
AU  - Allen TM
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
FAU - Chodosh, James
AU  - Chodosh J
AUID- ORCID: 0000-0002-7463-1599
AD  - Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA.
FAU - Walker, Bruce D
AU  - Walker BD
AUID- ORCID: 0000-0001-6122-9245
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. 
      bwalker@mgh.harvard.edu.
AD  - The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
AD  - Institute for Medical Engineering and Science, Massachusetts Institute of 
      Technology, Cambridge, MA 02139, USA.
LA  - eng
GR  - UM1 AI100663/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - U19 AI067854/AI/NIAID NIH HHS/United States
GR  - P01 AI104715/AI/NIAID NIH HHS/United States
GR  - P30 AI060354/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (AIDS Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B57 antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Proteome)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
SB  - IM
CIN - Science. 2019 May 3;364(6439):438-439. PMID: 31048479
MH  - AIDS Vaccines/*genetics/*immunology
MH  - Acquired Immunodeficiency Syndrome/*prevention & control
MH  - Alleles
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Conserved Sequence
MH  - Epitopes, T-Lymphocyte/*genetics/*immunology
MH  - HIV-1/*immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - Histocompatibility Antigens Class I/genetics/immunology
MH  - Humans
MH  - Mutation
MH  - Proteome/genetics/immunology
MH  - Virus Replication
MH  - gag Gene Products, Human Immunodeficiency Virus
PMC - PMC6855781
MID - NIHMS1055203
COIS- Competing interests: G.D.G., E.J.R., and B.D.W. have filed a provisional patent 
      application (62/817,094).
EDAT- 2019/05/03 06:00
MHDA- 2019/11/02 06:00
PMCR- 2019/11/14
CRDT- 2019/05/04 06:00
PHST- 2018/09/23 00:00 [received]
PHST- 2019/03/25 00:00 [accepted]
PHST- 2019/05/04 06:00 [entrez]
PHST- 2019/05/03 06:00 [pubmed]
PHST- 2019/11/02 06:00 [medline]
PHST- 2019/11/14 00:00 [pmc-release]
AID - 364/6439/480 [pii]
AID - 10.1126/science.aav5095 [doi]
PST - ppublish
SO  - Science. 2019 May 3;364(6439):480-484. doi: 10.1126/science.aav5095.