SEQUENCE NOTES Molecular Characterization of the Human T Cell Lymphotropic Virus Type 2 Long Terminal Repeat Region: A Discussion about Possible Influences at Viral Gene Expression Fernanda K. Barreto, 1 Felipe F.A. Rego, 1 Loianna M. Fonseca, 1 Bernardo Galva ˜ o-Castro-Filho, 2 Thessika H.A. Arau ´ jo, 1 Aline Cristina A. Mota-Miranda, 2,3 Joana P. Monteiro-Cunha, 2,3 and Luiz Carlos J. Alcantara 1 Abstract This study aimed to identify nucleotide signatures in the promoter region of human T cell lymphotropic virus type 2 (HTLV-2) isolated from infected individuals from Salvador, Brazil and in sequences from the GenBank database. DNA samples from HTLV-2-infected individuals were submitted to nested polymerase chain reaction (PCR) and sequencing, and molecular analyses were performed using bioinformatics tools. The phylogeny of HTLV-2 strains isolated from patients from Salvador reveals that all sequences were subtype c. One hundred and fifty-one sequences from GenBank were selected, among which 30 belong to subtype a, 88 to subtype b, 32 to subtype c, and one to subtype d. Subtype-specific signatures were identified as well as mutations resulting in loss or gain of motifs important to transcription regulation. The subtypes a and b have two E box motifs, while subtypes c and d have only one. These polymorphisms may impact viral fitness and infection outcome and should be more closely investigated. H uman T cell lymphotropic virus type 2 (HTLV-2) was described in 1982. 1 Currently this virus is found mainly among Brazilian Amerindians, African populations, and in- travenous drug users (IVDU) from the United States, Europe, and Asia. 2 HTLV-2 is not clearly identified as the etiologic agent of human pathologies, although it seems to be linked to neurological disorders and appears to be associated with an increased incidence of autoimmune diseases and respiratory tract infections. 3,4 Viral and host factors are probably involved in determining the infection outcome. It is believed that small variations in the HTLV-2 long terminal repeat (LTR) region may modify the binding ability of transcription factors and this could in- fluence gene expression. Although most of the HTLV-2 genome remains stable, considerable variations are noted in the promoter region of this retrovirus. Phylogenetic analysis, using this region and the env gene, demonstrated three main subtypes of HTLV-2: HTLV-2a, HTLV-2b, 5 and HTLV-2d. 6 In addition, one cluster within subtype a, formed exclusively by viral isolates from Brazil, was described in 1996, and it is called HTLV-2c. 7 De- spite this genetic variability, to date there are no reports de- scribing nucleotide signatures specific to the viral subtypes or evaluating the consequences of nucleotide variations at the gene expression. Therefore, this study was performed with the objective of identifying nucleotide variations (signatures) in the HTLV-2 promoter region of isolates from different geographic regions and from different viral subtypes. Blood samples were collected from 15 infected individuals followed at the HTLV reference center of Bahia School of Medicine and Public Health, located in Salvador city, North- eastern Brazil. All patients were monoinfected with HTLV-2. The Ethnic Committee of Centro de Pesquisa Goncalo Moniz/ FIOCRUZ approved this study. Informed consent was ob- tained from all patients. DNA was extracted using a spin column QIAamp DNA Blood Minikit (Qiagen) following the manufacturer’s 1 Laborato ´ rio Hematologia, Gene ´tica e Biologia Computacional, Centro de Pesquisa Gonc ¸alo Moniz, Fundac ¸a ˜ o Oswaldo Cruz, Salvador, Bahia, Brazil. 2 Escola Bahiana de Medicina e Sau ´de Pu ´ blica, Salvador, Bahia, Brazil. 3 Universidade Federal da Bahia, Instituto de Cie ˆncias da Sau ´ de, Salvador, Bahia, Brazil. AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 30, Number 1, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2013.0181 92