Discovery and characterization of auxiliary proteins encoded by type 3 simian T-cell lymphotropic viruses.
Discovery and characterization of auxiliary proteins encoded by type 3 simian T-cell lymphotropic viruses.
复制标题
3 型猿猴 T 细胞嗜淋巴细胞病毒编码的辅助蛋白的发现和表征。
DOI：
10.1128/jvi.02150-14
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发表时间：
2015
影响因子：
5.4
通讯作者：
Mahieu
中科院分区：
文献类型：
--
作者：
Turpin,Jocelyn;Journo,Chloé;Ko,NgaLing;Sinet,Flore;Carpentier,Alexandre;Galioot,Amandine;Edwards,Dustin;Vandamme,Anne-Mieke;Gazzolo,Louis;DucDodon,Madeleine;Gessain,Antoine;Kashanchi,Fatah;Balansard,Ivan;Lacoste,Romain;Mahieu
Human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 encode auxiliary proteins that play important roles in viral replication, viral latency, and immune escape. The presence of auxiliary protein-encoding open reading frames (ORFs) in HTLV-3, the latest HTLV to be discovered, is unknown. Simian T-cell lymphotropic virus type 3 (STLV-3) is almost identical to HTLV-3. Given the lack of HTLV-3-infected cell lines, we took advantage of STLV-3-infected cells and of an STLV-3 molecular clone to search for the presence of auxiliary transcripts. Using reverse transcriptase PCR (RT-PCR), we first uncovered the presence of three unknown viral mRNAs encoding putative proteins of 5, 8, and 9 kDa and confirmed the presence of the previously reportedRorfIItranscript. The existence of these viral mRNAs was confirmed by using splice site-specific RT-PCR withex vivosamples. We showed that p5 is distributed throughout the cell and does not colocalize with a specific organelle. The p9 localization is similar to that of HTLV-1 p12 and induced a strong decrease in the calreticulin signal, similarly to HTLV-1 p12. Although p8, RorfII, and Rex-3 share an N-terminal sequence that is predicted to contain a nucleolar localization signal (NoLS), only p8 is found in the nucleolus. The p8 location in the nucleolus is linked to a bipartite NoLS. p8 and, to a lesser extent, p9 repressed viral expression but did not alter Rex-3-dependent mRNA export. Using a transformation assay, we finally showed that none of the STLV-3 auxiliary proteins had the ability to induce colony formation, while both Tax-3 and antisense protein of HTLV-3 (APH-3) promoted cellular transformation. Altogether, these results complete the characterization of the newly described primate T-lymphotropic virus type 3 (PTLV-3).IMPORTANCETogether with their simian counterparts, HTLVs form the primate T-lymphotropic viruses. HTLVs arose from interspecies transmission between nonhuman primates and humans. HTLV-1 and HTLV-2 encode auxiliary proteins that play important roles in viral replication, viral latency, and immune escape. The presence of ORFs encoding auxiliary proteins in HTLV-3 or STLV-3 genomes was unknown. Usingin silicoanalyses,ex vivosamples, orin vitroexperiments, we have uncovered the presence of 3 previously unknown viral mRNAs encoding putative proteins and confirmed the presence of a previously reported viral transcript. We characterized the intracellular localization of the four proteins. We showed that two of these proteins repress viral expression but that none of them have the ability to induce colony formation. However, both Tax and the antisense protein APH-3 promote cell transformation. Our results allowed us to characterize 4 new retroviral proteins for the first time.
