PMID- 21124229
OWN - NLM
STAT- MEDLINE
DCOM- 20110216
LR  - 20220129
IS  - 1944-7884 (Electronic)
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 56
IP  - 2
DP  - 2011 Feb 1
TI  - Reduced replication capacity of NL4-3 recombinant viruses encoding reverse 
      transcriptase-integrase sequences from HIV-1 elite controllers.
PG  - 100-8
LID - 10.1097/QAI.0b013e3181fe9450 [doi]
AB  - BACKGROUND: Identifying viral and host determinants of HIV-1 elite control may 
      help inform novel therapeutic and/or vaccination strategies. Previously, we 
      observed decreased replication capacity in controller-derived viruses suggesting 
      that fitness consequences of human leukocyte antigen (HLA) class I-associated 
      escape mutations in Gag may contribute to this phenotype. This study examines 
      whether similar functional defects occur in Pol proteins of elite controllers. 
      METHODS: Recombinant NL4-3 viruses encoding plasma RNA-derived reverse 
      transcriptase-integrase sequences from 58 elite controllers and 50 untreated 
      chronic progressors were constructed, and replication capacity measured in vitro 
      using a green fluorescent protein (GFP) reporter T-cell assay. Sequences were 
      analyzed for drug resistance and HLA-associated viral polymorphisms. RESULTS: 
      Controller-derived viruses displayed significantly lower replication capacity 
      compared with those from progressors (P < 0.0001). Among controllers, the most 
      attenuated viruses were generated from individuals expressing HLA-B*57 or B*51. 
      In viruses from B*57+ progressors (n = 8), a significant inverse correlation was 
      observed between B*57-associated reverse transcriptase-integrase escape mutations 
      and replication capacity (R = -0.89; P = 0.003); a similar trend was observed in 
      B*57+ controller-derived viruses (n = 20, R = -0.36; P = 0.08). CONCLUSIONS: 
      HIV-1 Pol function seemed to be compromised in elite controllers. As observed 
      previously for Gag, HLA-associated immune pressure in Pol may contribute to viral 
      attenuation and subsequent control of viremia.
FAU - Brumme, Zabrina L
AU  - Brumme ZL
AD  - Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
FAU - Li, Chun
AU  - Li C
FAU - Miura, Toshiyuki
AU  - Miura T
FAU - Sela, Jennifer
AU  - Sela J
FAU - Rosato, Pamela C
AU  - Rosato PC
FAU - Brumme, Chanson J
AU  - Brumme CJ
FAU - Markle, Tristan J
AU  - Markle TJ
FAU - Martin, Eric
AU  - Martin E
FAU - Block, Brian L
AU  - Block BL
FAU - Trocha, Alicja
AU  - Trocha A
FAU - Kadie, Carl M
AU  - Kadie CM
FAU - Allen, Todd M
AU  - Allen TM
FAU - Pereyra, Florencia
AU  - Pereyra F
FAU - Heckerman, David
AU  - Heckerman D
FAU - Walker, Bruce D
AU  - Walker BD
FAU - Brockman, Mark A
AU  - Brockman MA
LA  - eng
GR  - AI028568/AI/NIAID NIH HHS/United States
GR  - R01 AI028568-20/AI/NIAID NIH HHS/United States
GR  - CAPMC/CIHR/Canada
GR  - AI030914/AI/NIAID NIH HHS/United States
GR  - R37 AI028568/AI/NIAID NIH HHS/United States
GR  - R01 AI030914-16/AI/NIAID NIH HHS/United States
GR  - R01 AI028568/AI/NIAID NIH HHS/United States
GR  - P30 AI060354/AI/NIAID NIH HHS/United States
GR  - R01 AI030914/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - EC 2.7.7.- (HIV Integrase)
RN  - EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - YY6481J2FF (p31 integrase protein, Human immunodeficiency virus 1)
SB  - IM
MH  - HIV Infections/*virology
MH  - HIV Integrase/*genetics
MH  - *HIV Long-Term Survivors
MH  - HIV Reverse Transcriptase/*genetics
MH  - HIV-1/genetics/isolation & purification/*physiology
MH  - Humans
MH  - Mutation
MH  - *Recombination, Genetic
MH  - Virulence
MH  - *Virus Replication
PMC - PMC3078702
MID - NIHMS252797
EDAT- 2010/12/03 06:00
MHDA- 2011/02/17 06:00
PMCR- 2011/08/01
CRDT- 2010/12/03 06:00
PHST- 2010/12/03 06:00 [entrez]
PHST- 2010/12/03 06:00 [pubmed]
PHST- 2011/02/17 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - 10.1097/QAI.0b013e3181fe9450 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):100-8. doi: 
      10.1097/QAI.0b013e3181fe9450.