[Biological characteristics of HIV-1 isolates circulating in China are linked to its env V3 loop sequence variability].
OBJECTIVE
To investigate the biological characteristics of the HIV-1 isolates circulating in China and to define the association of these properties with env V3 loop sequence variability.


METHODS
Primary viruses were isolated from fresh peripheral blood mononuclear cells (PBMCs) using the traditional co-culture method and their capacity of inducing syncytium was tested in MT-2 cells; meanwhile, their coreceptor usage was determined with GHOST-cell lines which stably express CD4 and the chemokine receptor CCR5 or CXCR4. Furthermore, HIV-1 V3 and its flanking region sequences were amplified by nest-polymerase chain reaction (nest-PCR) and sequenced. A GCG software was used to translate the DNA sequences into polypeptide sequences.


RESULTS
Five primary viral strains were isolated from 3 different regions in China. The isolates LTG0213 and LTG0214 induced syncytia in MT-2 cells and used CXCR4 as coreceptor. The isolates XJN0021, XJN0091, and SHXDC0041 did not induce syncytia and used CCR5 as coreceptor. There were obvious differences between X4/SI and R5/NSI viruses in env V3 loop sequences. A consensus motif at the positions 8, 11, 18, and 25 in V3 loop was identified as follows: a sequence as "8-TXXS/GXXXXXXR/QXXXXXXE/D-25" will predict the usage of CCR5 coreceptor; a sequence replacing these positions with basic amino acids (except position 25) will very likely predict the usage of CXCR4 coreceptor.


CONCLUSIONS
The biological characteristics of HIV isolates are linked to env V3 loop sequence variability: introducing basic amino acids (or translating from acidic amino acids into neutral amino acids) at the positions 8, 11, 18, and 25 in V3 loop will change viral strain's biological phenotype from NSI/CCR5 to SI/CXCR4. The biological phenotype of HIV-1 can be predicted with V3 loop sequence analysis.
Hei
Fa-xin
FX
Department of Virology and Immunology, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Hong
Kun-xue
KX
Song
Yan-hui
YH
Tang
Hai-li
HL
Peng
Hong
H
Xu
Jian-qing
JQ
Xing
Hui
H
Shao
Yi-ming
YM
D002681:China; D018920:Coculture Techniques / Q000379:methods; D004252:DNA Mutational Analysis; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D014779:Virus Replication
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4