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Prevalence of HIV-1 CCR5 Co-Receptor Tropism Differs by Env (gp41) Subtype in a Large Commercial Dataset
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Reported by Jules Levin
ICAAC Sept 11-15 2009
San Francisco
Eric Stawiski1, Mojgan Haddad1, Sergei Pond2, Laura
Napolitano1, Chris Petropoulos1, Eoin Coakley1, Jeannette
Whitcomb1
1Monogram Biosciences,
South San Francisco
CA USA.
2University of California, San Diego
BACKGROUND
Determination of HIV-1 subtype is important for epidemiological studies and could add scientific value to co-receptor tropism (CRT) determination.
The GP41 region is more conserved than the GP120 region of envelope making this region suitable for high throughput population based sequencing.
Previous work has shown that the GP41 region of envelope provides a powerful approach for determination of subtype in group M viruses1.
CRT is known to vary by subtype however large databases have not been fully utilized to characterize CRT determined using the same assay.
Here we show that prevalence of R5 CRT varies by env subtype within a commercial dataset.
METHODS
An average of 797 nucleotides per sample were determined in the gp41 region of env for commercial samples (Fig. 1).
The HYPHY SCUEAL2 package was used for determination of HIV-1 env subtype and samples with a subtype support of 0.5 or better were selected.
Enhanced Trofile was used to determine CRT.
Fishers Exact Test was used to compare the prevalence of R5 to non-R5 (DM and X4) CRT.
Comparisons of subtype and CRT were made by region (USA compared to Europe and South America).
ABBREVIATIONS
CRT = co-receptor tropism
R5 = CCR5 tropic
X4 = CXCR4 tropic
DM = Dual and/or mixed tropic
RESULTS
We determined subtypes and CRT for over 18,000 commercial samples.
Samples from Europe had a higher prevalence of R5 CRT compared to the USA at 68% vs. 56% respectively (P< 0.001) (Fig. 2).
Samples from South America had a significantly lower prevalence of R5 CRT compared to the USA at 47% vs. 56% (P < 0.001) (Fig. 2).
Subtype composition varied by region with subtype B making up 97% in the USA and 85% in Europe. Samples from Europe showed a higher percentage of subtype C, G, A/G, F1, A and D (in that order) when compared to the USA (Fig. 3).
Among B subtypes, R5 CRT was predominant (59%, N=10,008). Relative to subtype B, R5 CRT was significantly more common in subtypes A, A1, A/G, C, G at 81% (N=83), 83% (N=78), 70% (N=120), 85% (N=317) and 85% (N=104), respectively (P
Subtype D samples showed more frequent CXCR4-usage relative to subtype B (P = 0.03, 46% R5, 44% DM, 10% X4, N=59) (Fig. 4, Table 1).
CONCLUSIONS
The prevalence of R5 CRT varies by env subtype.
The addition of HIV env subtype to Trofile CRT profiling may augment future epidemiologic studies and provide a useful context in which to interpret HIV tropism data.
For quality control purposes we sequence a subset of
commercial samples in the gp41 region of envelope as
depicted above in an annotated representation of HXB2.
REFERENCES
1. Pieniazek, D., C. Young, and R. B. Lal. 1998. Phylogenetic analysis of the gp41 envelope of HIV-1 groups M, N, and O strains provides an alternate region for subtype determination, p. III112-III118. Human retroviruses and AIDS 1998
2. http://www.hyphy.org/pubs/SCUEAL/
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