Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients

Autor: Edna Aoba Yassui Ishikawa, Carlos Araújo da Costa, Ingrid Christiane Silva, Cássia Cristine Costa Pereira, Marcos William Leão de Araújo, Danilo Souza de Almeida, Edivaldo Costa, Bruna Teles Pinheiro, Akim Felipe Santos Nobre, Louise de Souza Canto Ferreira, Stephen F. Ferrari, Mariza da Silva Borges, Maísa Silva de Sousa, Maria de Nazaré do Socorro de Almeida Viana
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Mutation rate
Endemic Diseases
viruses
Mutant
Retroviridae Proteins
Oncogenic
Gene Expression
medicine.disease_cause
Genetic diversity
Nucleotide diversity
Genotype
Mutation
Human T-lymphotropic virus 1
Middle Aged
Infectious Diseases
Neglected diseases
Female
Brazil
Adult
medicine.medical_specialty
Heterozygote
V?rus 1 Linfotr?pico T Humano / patogenicidade
030106 microbiology
Pain
Primary Dysautonomias
Biology
Virus
lcsh:Infectious and parasitic diseases
Evolu??o Molecular
03 medical and health sciences
Protein Domains
Virology
Molecular genetics
medicine
Rea??o em Cadeia da Polimerase / m?todos
Humans
lcsh:RC109-216
Gene
Retrospective Studies
Base Sequence
Research
Computational Biology
Gene Products
env
Bayes Theorem
Doen?as Negligenciadas
Sequence Analysis
DNA
HTLV-I Infections
030104 developmental biology
Varia??o Gen?tica / gen?tica
Amino Acid Substitution
Molecular evolution
Zdroj: Virology Journal, Vol 15, Iss 1, Pp 1-10 (2018)
Virology Journal
Repositório Digital do Instituto Evandro Chagas (Patuá)
Instituto Evandro Chagas (IEC)
instacron:IEC
DOI: 10.1186/s12985-018-0984-9
Popis: This research was supported by the UFPA Pro-Rectory for Extension and the Brazilian National Council for Research and Development ? CNPq (MCTI/ CNPQ/Universal 14/2014 _PROJ_459352/2014?8). Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. Faculty of Pharmacy. Bel?m, PA, Brazil. Universidade Federal do Par?. Faculty of Nursing. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. Universidade Federal de Sergipe. Department of Ecology. S?o Crist?v?o, SE, Brazil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Postgraduate Program in Tropical Diseases. Bel?m, PA, Brazil. BACKGROUND: The human T-lymphotropic virus type 1 (HTLV-1) affects 2-5 million people worldwide, and is associated with a number of degenerative and infectious diseases. The Envelope glycoproteins (gp) are highly conserved among the different HTLV-1 isolates, although nucleotide substitutions in the region that codifies these proteins may influence both the infectivity and the replication of the virus. The gp46 gene has functional domains which have been associated with the inhibition of the formation of the syncytium, cell-cell transmission, and the production of antibodies. The present study investigated the genetic stability of the gp46 gene of HTLV-1 in an endemic region of Brazilian Amazonia. METHODS: Index case (IC - a sample of a given family group) carriers of HTLV-1 were investigated in the metropolitan region of Bel?m (Par?, Brazil) between January 2010 (registered retrospectively) and December 2015. The sequences that codify the gp46 were amplified by PCR, purified and sequenced (MF084788-MF084825). The gene was characterized using bioinformatics and Bayesian Inference. RESULTS: The 40 patients analyzed had a mean age of 45.2 years and 70% presented some type of symptom, with a predominance of pain and sensitivity, dysautonomia, and motor disorders. All patients presented the aA (Transcontinental Cosmopolitan) genotype, with an extremely low mutation rate, which is characteristic of the codifying region (aA - 1.83???10-4 mutations per site per year). The gp46 gene had a nucleotide diversity of between 0.00% and 2.0%. Amino acid mutations were present in 66.6% of the samples of individuals with signs/symptoms or diseases associated with HTLV-1 (p?=?0.0091). Of the three most frequent mutations, the previously undescribed N93D mutant was invariably associated with symptomatic cases. CONCLUSIONS: The aA HTLV-1 subtype is predominant in the metropolitan region of Bel?m and presented a high degree of genetic stability in the codifying region. The rare N93D amino acid mutation may be associated with the clinical manifestations of this viral infection. IMPORTANCE: Little is known of the phylogeny of HTLV-1 in the endemic region of Brazilian Amazonia, and few complete gene sequences are available for the gp46 glycoprotein from the local population. The nucleotide sequences of the viral gp46 gene recorded in the present study confirmed the genetic stability of the region, and pointed to a homogeneous viral group, with local geographic characteristics. Further research will be necessary to more fully understand the molecular diversity of this protein, given the potential of this codifying region as a model for an effective HTLV-1 vaccine. The identification of a rare mutation (N93D), present only in symptomatic patients, should also be investigated further as a potential clinical marker.
Databáze: OpenAIRE
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