Caracterização molecular do HTLV-1: impacto no desenvolvimento de doenças associadas

Abstract

Background: HTLV-1 is a globally distributed pathogen that affects approximately 5 to 10 million people. It is estimated that Brazil has about 800,000 people living with the virus, which characterizes it as one of the countries with the highest absolute number of cases. In Brazil, the North and Northeast regions are the most affected by the virus. HTLV-1 infection can lead to the development of diseases such as ATLL, HAM/TSP and IDH. The HTLV-1 genome has structural genes and a region responsible for encoding accessory and regulatory proteins, important for the establishment, dissemination, and action of the virus. The sequencing of this genome can elucidate factors of this virus that influence the spread and development of clinical manifestations associated with HTLV-1. Objective: The main objective of this work is to evaluate the role of mutations in the HTLV-1 genome and its possible association with the development of HTLV-1-associated diseases. Methods: Cross-sectional study, with samples from individuals infected with HTLV-1, which were sequenced to identify mutations in the LTR and hbz regions of the virus genome. In addition, two systematic reviews were performed following the PRISMA instructions for deepening and reviewing the study areas. Results: Two mutations, V15M and R119Q, were observed in the hbz region, with V15M observed exclusively in HAM/TSP patients, while R119Q appears to be a protective factor for the development of the disease. In LTR, mutations were found that led to the appearance or deletion of transcription factor binding sites. In addition, one of the systematic reviews found four studies that associated mutations in env and ORF-1 with the development of some clinical form. Regarding the sequencing study, the Sanger methodology is more used for the study of HTLV-1. Conclusions: It was possible to observe the presence of mutations related to the development of HAM/TSP, such as C39Y, P45L, S69G, P86S and R88K (ORF-I), S72G and N93D (gp46) and V15M and R119Q (HBZ). Alterations in transcription factor binding sites were also observed, which may be related to an imbalance in the production and expression of viral genes. In addition, it was possible to observe that despite advances in sequencing technologies, HTLV-1 studies still work with the first generation of sequencing, Sanger.