PMID- 28500742
OWN - NLM
STAT- MEDLINE
DCOM- 20180405
LR  - 20190106
IS  - 1096-9071 (Electronic)
IS  - 0146-6615 (Linking)
VI  - 89
IP  - 10
DP  - 2017 Oct
TI  - Amino acids at positions 3, 168, and 169 are associated with the ability of Nef 
      proteins from HIV-1 CRF01_AE to downmodulate CD4.
PG  - 1788-1795
LID - 10.1002/jmv.24851 [doi]
AB  - Several HIV-1 subtypes are co-circulating among various high-risk groups in 
      China, and an increasing prevalence of CRF01_AE was observed among MSM (men who 
      have sex with men) within recent years. Patients infected with CRF01_AE may 
      experience a more rapid disease progression than patients infected with 
      non-CRF01_AE; however, the underlying mechanisms remains elusive. HIV-1 Nef is a 
      multifunctional protein and plays critical roles in viral pathogenesis. Nef 
      downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission 
      and escape from the host immune response. In this study, we investigated the CD4 
      downmodulation activity of Nef proteins isolated from HIV-1 CRF01_AE and analyzed 
      a potential relationship of Nef's capacity to downregulate CD4 with disease 
      progression. We found that the majority of these Nefs from HIV-1 CRF01_AE 
      efficiently downregulated CD4; Nefs with weaker CD4 downmodulation activity 
      tended to be associated with higher CD4 levels and lower viral loads. Further 
      elucidation revealed that amino acid residues at positions 3, 168, and 169 of 
      CRF01_AE Nefs were associated with the capacity to downregulate CD4. Our data 
      suggest that the capacity of Nef-mediated CD4 downregulation is not the only 
      determinant for controlling disease progression, and other host and viral factors 
      should be considered to explain the rapid disease progression of patients 
      infected with HIV-1 CRF01_AE.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Kuang, Wen-Dong
AU  - Kuang WD
AD  - CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of 
      Shanghai, Chinese Academy of Sciences, Shanghai, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Zhou, Yan-Heng
AU  - Zhou YH
AD  - CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of 
      Shanghai, Chinese Academy of Sciences, Shanghai, China.
FAU - Zhong, Ping
AU  - Zhong P
AD  - Department of AIDS and STD, Shanghai Municipal Center for Disease Control and 
      Prevention, Shanghai, China.
FAU - Zhang, Chiyu
AU  - Zhang C
AD  - CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of 
      Shanghai, Chinese Academy of Sciences, Shanghai, China.
FAU - Wang, Jian-Hua
AU  - Wang JH
AUID- ORCID: 0000-0002-6435-9907
AD  - CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of 
      Shanghai, Chinese Academy of Sciences, Shanghai, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170710
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Amino Acids)
RN  - 0 (CD4 Antigens)
RN  - 0 (Gene Products, nef)
SB  - IM
MH  - Amino Acids/*chemistry
MH  - CD4 Antigens/*genetics/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - China/epidemiology
MH  - Disease Progression
MH  - Down-Regulation
MH  - Gene Products, nef/genetics/*metabolism
MH  - HIV Infections/immunology/transmission/*virology
MH  - HIV-1/*chemistry/genetics/*immunology/pathogenicity
MH  - HeLa Cells
MH  - Humans
MH  - Male
MH  - Viral Load
OTO - NOTNLM
OT  - CD4
OT  - HIV-1
OT  - Nef
EDAT- 2017/05/14 06:00
MHDA- 2018/04/06 06:00
CRDT- 2017/05/14 06:00
PHST- 2017/02/20 00:00 [received]
PHST- 2017/04/24 00:00 [accepted]
PHST- 2017/05/14 06:00 [pubmed]
PHST- 2018/04/06 06:00 [medline]
PHST- 2017/05/14 06:00 [entrez]
AID - 10.1002/jmv.24851 [doi]
PST - ppublish
SO  - J Med Virol. 2017 Oct;89(10):1788-1795. doi: 10.1002/jmv.24851. Epub 2017 Jul 10.