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

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-1exposed-seronegative (HTLV-2/HIV-1ESN) individuals, 7 LTNP-HIV-1/HTLV-2-co-infected and 8 LTNP-HIV-1mono-infected subjects

Analysis of colorectal cancers for human cytomegalovirus presence

<p>Abstract</p> <p>Background</p> <p>A possible association between human cytomegalovirus (HCMV) infection and colorectal cancer progression has been inferred by the identification in tumour tissues of HCMV antigens and specific viral DNA or RNA sequences. To further investigate the relationship between HCMV and colorectal cancers we developed qualitative and quantitative PCR assay to detect HCMV DNA in 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients belonging to 4 different histological phenotypes: adenoma; poorly, moderately and well differentiated adenocarcinomas.</p> <p>Results</p> <p>Of the 56 FFPE tested tissue samples, 6 (11%) were positive for HCMV nested PCR amplification, and more precisely 1 (5%) of 20 cases of adenoma and 5 (21%) of 24 cases of moderately differentiated adenocarcinoma. No PCR positivity was obtained in samples from well and poorly differentiated adenocarcinomas.</p> <p>Conclusion</p> <p>Our observations suggest that there is no evidence of a direct association between HCMV and colorectal cancer. Moreover, the results obtained are not supportive of a causal role of HCMV in the processes of carcinogenesis and/or progression of colorectal cancer. However, the fact that the virus may present a "hit and run" like-mechanism and HCMV can thus only be detectable at a particular stage of a processing adenocarcinoma, suggests that a significant number of colorectal cancers might have been the subject of HCMV infection that could contribute to trigger the oncogenic differentiation. Our analysis does not exclude the possibility of HCMV infection subsequent viral clearance.</p

The MHC-II transactivator CIITA, a viral restriction factor inhibiting the replication of Human T-Cell Lymphotropic Virus Type 1

publishedVersio

Analysis of temporal expression of HTLV-2 reveals similarities and functional differences from HTLV-1

In the present study, we developed a robust splice site-specific real-time RT-PCR method to quantitate all HTLV-2 transcripts. Results of this analysis conducted on three different infected cell lines (HTLV-2A Mo-T , C344 and HTLV-2B BJAB-Gu) showed that the most abundant mRNA was gag/pol followed by the accessory transcript 1-3, coding for the p28 and for p22/p20 proteins. The third most abundant mRNA was tax/rex. To investigate if different mRNAs produced by HTLV-2 are expressed at different levels upon viral reactivation, we studied the kinetics of viral expression in PBMCs from three subjects infected with HTLV-2B and cultured in vitro for 48 hours. The level of expression of the full length gag/pol transcript was the highest in all samples. The tax/rex mRNA was detected already at time zero and increased very rapidly following in vitro culture, reaching the highest copy number between zero and 2-4 hours. The minus-strand APH-2 mRNA, was expressed at high level. As observed in the infected cell lines, the 1-3 mRNA was expressed at high levels in all subjects. This finding is particularly intriguing, as it encodes two proteins that were shown to exert a powerful control on Tax and Rex function. This peculiar pattern of expression, which is in striking contrast with that of HTLV-1, might in part explain the differential pathogenicity of the two viruses

Cytoplasmic and nuclear events controlling Tax-mediated activation of the NF-κB pathway: involvement of TAB2, IKKgamma/NEMO and calreticulin

The Tax oncoprotein of HTLV-1 initiates T-cell transformationby dysregulating cell cycle progression andinhibiting DNA damage responses. The subsequentgenomic instability might result in constitutive activationof the NF-B pathway observed in HTLV-1-transformedT lymphocytes. Our previous results indicatedthat differential modifications of Tax by ubiquitinationor sumoylation controlled its retention either in thecytoplasm or in the nucleus, respectively. Here we showthat Tax is targeted to pre-existing punctate cytoplasmicstructures which contain the TNF-receptor associatedprotein 2 (TAB2)

Comparative analysis of HTLV-1 and HTLV-2 post-translational modifications of Tax proteins in relation to their intracellular localization and activation of gene expression

Poster presentatio

IKKepsilon involvement in Tax-mediated activation of INF pathway

HTLV-1 Tax de-regulates several cellular signaling pathways leading to cell transformation by altering gene expression, intracellular protein distribution and cell proliferation. Tax-1 induces persistent activation of several transcriptional factors and signal transduction pathways, including NF-\u3baB and CREB/ATF. It is known that Tax-1 constitutively activates TAK1 (transforming growth factor-\u3b2-activated kinase 1) and modifies the interferon (INF) regulatory signals by controlling the expression of INF transcription factors 3 (INF3) and INF4. We have recently reported that HTLV-1 and HTLV-2 Tax proteins interact with TAK1-binding protein 2 (TAB2) of the NF-\u3baB pathway and that both Tax proteins transactivate NF-\u3baB promoters [1]. TAB2 functions as an adaptor protein to recruit TAK1 to TRAF2 (TNF-\u3b1 receptor-associated factor) in TNF-\u3b1 signaling pathways. In the present study we have investigated Tax-1 and Tax-2 role in modifying INF and NF-\u3baB activation through the recruitment of IKKepsilon, an I\u3baB kinase homologue involved in NF-\u3baB and INF3 signaling pathways. By co-immunoprecipitation experiments, we have found that both IKKepsilon and Tax-1, but not Tax-2, are present in protein complexes in transfected cells. IKKepsilon and Tax-1 or Tax-2 role in the activation of INF responsive elements or NF-\u3baB containing promoters have been analyzed after transfecting the protein genes in 293T cells and measuring the effect by luciferase assay. Co-expression of Tax-1 and IKKepsilon resulted in an increased IRF activation mediated by IKKepsilon. Interaction of IKKepsilon with Tax-1 and Tax-2 and their possible effects in the de-regulation of the IRF3 pathways will be discussed