p30 protein: a critical regulator of HTLV-1 viral latency and host immunity

• Published in: Retrovirology 2019-12, Vol.16 (1), p.42-42, Article 42
• Main Authors: Moles, Ramona, Sarkis, Sarkis, Galli, Veronica, Omsland, Maria, Purcell, Damian F J, Yurick, David, Khoury, Georges, Pise-Masison, Cynthia A, Franchini, Genoveffa
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adult T-cell leukemia/lymphoma; Amino acids; Animals; Apoptosis; ATLL; Biological response modifiers; Cell adhesion & migration; Cell cycle; Cell Line; Cytoplasm; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Enzymes; Gene Expression; Gene Expression Regulation, Viral; Gene mutation; Genes; Genomes; Genomics; Genotype; Genotypes; Health; Health aspects; HTLV-1; HTLV-I Infections - immunology; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - immunology; Human T-lymphotropic virus 1 - physiology; Humans; Hypotheses; Immune response; Indigenous peoples; Infection; Infections; Interferon; Kinases; Latency; Leukemia; Lymphocytes T; Lymphoma; Macaca - virology; Medical prognosis; Messenger RNA; Mutation; Myeloid cells; Nucleoli; orf-II; p30; p30 Protein; Point mutation; Post-transcription; Protein expression; Proteins; Regulatory proteins; Retroviridae Proteins - genetics; Retroviridae Proteins - immunology; Reversion; Review; RNA; RNA, Viral - genetics; Signal transduction; Spasticity; T cells; Tax-orf-II; Viral infections; Virus Latency - genetics; Viruses
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/s12977-019-0501-2

The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus's most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly spliced Tax-orf II mRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.