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137 In Vivo Expression of Cytokines and Chemokines and HIV-1 Disease Progression: Role of HTLV-II Coinfection
E. Vicenzi*1, C. Casoli2, S. Ghezzi1, U. Bertazzoni3, and G. Poli1
1San Raffaele Scientific Inst., Milan, Italy; 2Univ. of Parma, Italy; and 3Univ. of Verona, Italy
Background: Coinfection of HIV-1 and HTLV-II occurs in 10(13% of I.V. drug users in Europe. Conflicting results have been reported on the potential influence of HTLV-II coinfection on HIV-1 disease progression. We therefore investigated the patterns of CC-chemokine and cytokine expression in both mono- and coinfected individuals.
Methods: Relative quantification of cytokine and chemokine mRNA expression in unstimulated PBMC of individuals either singly infected or coinfected with HIV-1 and HTLV-II was carried out by Taqman-based real-time PCR. A cohort of LTNP was included in the study. Results were expressed as -fold difference vs. a reference RNA standard obtained from unstimulated PBMC of healthy uninfected individuals.
Results: In both mono- and coinfected individuals, IL-8 and IL-1beta expression was significantly up-regulated (approximately by 10-fold) in comparison with uninfected controls (p < 0.001). In contrast, IL-2, IL-15, and TNF-alpha levels were significantly down-regulated in coinfected individuals (p < 0.0005) and undetectable in HIV-1 mono-infected individuals. IL-4, IL-5, IL-10, and IL-12 were found similar in PBMC of both infected and uninfected individuals. IL-1alpha, IL-1beta? and IL-8 expression was significantly higher (p < 0.005) in individuals characterized by a high HIV-1/HTLV-II proviral DNA ratio and with advanced HIV-1 disease progression. Ex vivo, CD8+ T cells of HTLV-II-infected individuals inhibited HIV-1 replication via secretion of CC-chemokines, particularly MIP-1alpha. Of note, the levels of secreted MIP-1alpha were correlated with a high HTLV-II proviral DNA load in vivo. Since 2 isoforms of MIP-1alpha, LD78alpha and LD78beta, have been characterized, the latter being the most potent HIV-1 inhibitory chemokine, we are investigating whether a preferential expression of LD78beta is up-regulated by HTLV-II infection.
Conclusions: Up-regulation of certain pro-inflammatory cytokines (IL-1alpha/beta) and CXC-chemokines (IL-8) characterizes both HIV-1 and HTLV-II infections or coinfections, whereas HTLV-II up-regulates the expression of MIP-1alpha representing a potential mechanism of delayed HIV-1 disease progression in certain LTNP.
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