CXCR4-using HIV type 1 variants are more commonly found in peripheral blood mononuclear cell DNA than in plasma RNA.
OBJECTIVE
To compare the distribution of R5-like and X4-like HIV-1 envelope sequences in plasma and peripheral blood mononuclear cell (PBMC).


METHODS
Clonal sequencing of the HIV-1 glycoprotein 120 region was performed on PBMC DNA and plasma RNA of 11 HIV-1 subtype B-infected patients with high probability of carrying X4 virus. Coreceptor use was predicted using the position-specific scoring matrix (PSSM).


RESULTS
A total of 330 and 427 clonal envelope sequences were obtained from PBMC and plasma, respectively. PSSM interpretation revealed the presence of a mixture of predicted X4 and R5 sequences in 10 patients and pure R5 sequences in 1. The X4 sequences were significantly more represented in PBMC (with an average of 52.2% of the clonal proviral sequences scored X4) compared with plasma (19.7% X4 sequences) (P < 0.0001). At the single patient level, the higher representation of X4 sequences in PBMC reached statistical significance (P < 0.002) in 6 individuals.


CONCLUSIONS
Mixtures of X4 and R5 sequences with highly divergent PSSM scores are present in both plasma and PBMC, but a shift toward a more abundant representation of X4-like PSSM scores in PBMC-derived DNA was apparent. Additional studies are needed to evaluate the clinical importance of these findings with regard to tropism prediction and the use of CCR5 antagonists.
Verhofstede
Chris
C
Aids Reference Laboratory, Ghent University, Ghent, Belgium. chris.verhofstede@ugent.be
Vandekerckhove
Linos
L
Eygen
Veerle Van
VV
Demecheleer
Els
E
Vandenbroucke
Ina
I
Winters
Bart
B
Plum
Jean
J
Vogelaers
Dirk
D
Stuyver
Lieven
L
D000328:Adult; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000032:analysis / Q000097:blood / Q000235:genetics; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis / Q000097:blood / Q000235:genetics; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D019718:Receptors, CXCR4