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Updated: Jun 26, 2026
Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
CXCR4-using HIV type 1 variants are more commonly found in peripheral blood mononuclear cell DNA than in plasma RNA
Chris Verhofstede1, Linos Vandekerckhove, Veerle Van Eygen
1Aids Reference Laboratory, Ghent University, Ghent, Belgium. chris.verhofstede@ugent.be
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.
