PMID- 20042504
OWN - NLM
STAT- MEDLINE
DCOM- 20100402
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 84
IP  - 6
DP  - 2010 Mar
TI  - Evolution of the HIV-1 env gene in the Rag2-/- gammaC-/- humanized mouse model.
PG  - 2740-52
LID - 10.1128/JVI.02180-09 [doi]
AB  - Rag2(-/-) gamma(C)(-/-) mice transplanted with human hematopoietic stem cells 
      (DKO-hu-HSC mice) mimic aspects of human infection with human immunodeficiency 
      virus type 1 (HIV-1), including sustained viral replication and CD4(+) T-cell 
      decline. However, the extent of HIV-1 evolution during long-term infection in 
      these humanized mice, a key feature of the natural infection, has not been 
      assessed fully. In this study, we examined the types of genotypic and phenotypic 
      changes in the viral env gene that occur in the viral populations of DKO-hu-HSC 
      mice infected with the CCR5-tropic isolate HIV-1(JRCSF) for up to 44 weeks. The 
      mean rate of divergence of viral populations in mice was similar to that observed 
      in a cohort of humans during a similar period of infection. Many amino acid 
      substitutions were common across mice, including losses of N-linked glycosylation 
      sites and substitutions in the CD4 binding site and in CD4-induced epitopes, 
      indicating common selective pressures between mice. In addition, env variants 
      evolved sensitivity to antibodies directed at V3, suggesting a more open 
      conformation for Env. This phenotypic change was associated with increased CD4 
      binding efficiency and was attributed to specific amino acid substitutions. In 
      one mouse, env variants emerged that exhibited a CXCR4-tropic phenotype. These 
      sequences were compartmentalized in the mesenteric lymph node. In summary, viral 
      populations in these mice exhibited dynamic behavior that included sequence 
      evolution, compartmentalization, and the appearance of distinct phenotypic 
      changes. Thus, humanized mice offer a useful model for studying evolutionary 
      processes of HIV-1 in a complex host environment.
FAU - Ince, William L
AU  - Ince WL
AD  - Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular 
      Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
FAU - Zhang, Liguo
AU  - Zhang L
FAU - Jiang, Qi
AU  - Jiang Q
FAU - Arrildt, Kathryn
AU  - Arrildt K
FAU - Su, Lishan
AU  - Su L
FAU - Swanstrom, Ronald
AU  - Swanstrom R
LA  - eng
GR  - T32 AI007419/AI/NIAID NIH HHS/United States
GR  - T32-AI07419/AI/NIAID NIH HHS/United States
GR  - P30 CA016086/CA/NCI NIH HHS/United States
GR  - R37-AI44667/AI/NIAID NIH HHS/United States
GR  - P30-AI50410/AI/NIAID NIH HHS/United States
GR  - R37 AI044667/AI/NIAID NIH HHS/United States
GR  - R01-AI077454/AI/NIAID NIH HHS/United States
GR  - R01 AI077454/AI/NIAID NIH HHS/United States
GR  - P30-CA16086/CA/NCI NIH HHS/United States
GR  - P30 AI050410/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091230
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA, Viral)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 0 (RNA, Viral)
RN  - 0 (Rag2 protein, mouse)
RN  - 0 (env Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - DNA, Viral/genetics/immunology
MH  - DNA-Binding Proteins/genetics/*immunology
MH  - Disease Models, Animal
MH  - *Evolution, Molecular
MH  - HIV Infections/immunology
MH  - HIV-1/classification/*genetics/immunology
MH  - Humans
MH  - Interleukin Receptor Common gamma Subunit/genetics/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - RNA, Viral/genetics/immunology
MH  - Sequence Alignment
MH  - Viral Load
MH  - env Gene Products, Human Immunodeficiency Virus/*genetics
PMC - PMC2826074
EDAT- 2010/01/01 06:00
MHDA- 2010/04/03 06:00
PMCR- 2010/09/01
CRDT- 2010/01/01 06:00
PHST- 2010/01/01 06:00 [entrez]
PHST- 2010/01/01 06:00 [pubmed]
PHST- 2010/04/03 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - JVI.02180-09 [pii]
AID - 2180-09 [pii]
AID - 10.1128/JVI.02180-09 [doi]
PST - ppublish
SO  - J Virol. 2010 Mar;84(6):2740-52. doi: 10.1128/JVI.02180-09. Epub 2009 Dec 30.