Volume 2 Supplement 1

2005 International Meeting of The Institute of Human Virology

Open Access

HTLV-2 Induces Resistance to CCR5-Dependent HIV-1 Infection Via Selective PBMC Expression of CCL3L1

Retrovirology20052(Suppl 1):P119

https://doi.org/10.1186/1742-4690-2-S1-P119

Published: 8 December 2005

Background

In HIV-1/HTLV-2 co-infected IDUs the CCL3/MIP-1alpha induction by HTLV-2 leads to HIV inhibition. CCL3 gene codes for CCL3/LD78alpha and CCL3L1/LD78beta isoforms. CCL3L1 binds more potently to CCR5 than any other chemokine. Possession of a CCL3L1 copy number lower than two (the population average for Europeans) is associated with markedly enhanced HIV/AIDS susceptibility. Here, we analysed the genotype frequency of CCL3L1 and its expression in 8 HTLV-2-infected/HIV-1-exposed-seronegative (HTLV-2/HIV-1ESN) individuals, 7 LTNP-HIV-1/HTLV-2-co-infected and 8 LTNP-HIV-1-mono-infected subjects.

Methods

R5 HIV-1 infection of PBMC from HTLV-2/HIV-1ESN was evaluated for HIV proviral load and for p24 production. CCL3L1 gene copy number and mRNA expression levels were assessed using real-time PCR. CCL3 and CCL3L1 isoforms were identified from spontaneous PBMC cultures by mass spectrometry (MS).

Results

R5 infectibility and efficiency of viral replication in primary PBMC from HTLV-2/HIV-1ESN were very low. The median of CCL3L1 copy number was one in HTLV-2/HIV-1ESN, three in LTNP-HIV-1 and two in HIV-1/HTLV-2 subjects. CCL3-L1 mRNA was more abundant in individuals with HTLV-2 infection than in HIV-1 LTNPs. MS analysis evidenced that intact CCL3L1, usually not secreted from healthy subjects, was produced by PBMC of HTLV-2/HIV-1ESN. Noteworthy, CCL3L1 isoform was highly expressed by PBMC of LTNP HIV-1/HTLV-2, but not of HIV-1 LTNPs. The high CCL3L1 production, and a persistent IFN-gamma secretion, conferred a CCR5low phenotype to HTLV-2 infected subjects.

Conclusion

HTLV-2 may curtail HIV-1 infection upregulating the CCL3L1/LD78beta chemokine. Apparently, HTLV-2 infection can fully compensate for the functional state conferred by CCL3L1low.

Notes

Authors’ Affiliations

(1)
Dept. of Clinical Medicine, University of Parma
(2)
Dep. of Chemistry, University of Parma
(3)
University of Verona
(4)
DIBIT

Copyright

© The Author(s) 2005

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