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Human T-cell lymphotropic virus type 1 (HTLV-1) is mainly associated with two diseases: tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and adult T-cell leukaemia/lymphoma. This retrovirus infects five-10 million individuals throughout the world. Previously, we developed a database that annotates sequence data from GenBank and the present study aimed to describe the clinical, molecular and epidemiological scenarios of HTLV-1 infection through the stored sequences in this database. A total of 2,545 registered complete and partial sequences of HTLV-1 were collected and 1,967 (77.3%) of those sequences represented unique isolates. Among these isolates, 93% contained geographic origin information and only 39% were related to any clinical status. A total of 1,091 sequences contained information about the geographic origin and viral subtype and 93% of these sequences were identified as subtype “a”. Ethnicity data are very scarce. Regarding clinical status data, 29% of the sequences were generated from TSP/HAM and 67.8% from healthy carrier individuals. Although the data mining enabled some inferences about specific aspects of HTLV-1 infection to be made, due to the relative scarcity of data of available sequences, it was not possible to delineate a global scenario of HTLV-1 infection.

p. 1-10 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-06-25T17:58:22Z No. of bitstreams: 1 9999999999999999999ff.pdf: 959098 bytes, checksum: 50b03165d54f8297f87c9e137a48338f (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-26T13:17:19Z (GMT) No. of bitstreams: 1 9999999999999999999ff.pdf: 959098 bytes, checksum: 50b03165d54f8297f87c9e137a48338f (MD5) Made available in DSpace on 2013-11-26T13:17:19Z (GMT). No. of bitstreams: 1 9999999999999999999ff.pdf: 959098 bytes, checksum: 50b03165d54f8297f87c9e137a48338f (MD5) Previous issue date: 2013 Background: Human T-cell Leukemia Virus type 1 (HTLV-1) is the etiological agent of tropical spastic paraparesis/ HTLV-associated myelopathy (HAM/TSP) that can be identified in around 0.25%–3.8% of the infected population. Disease progression can be monitored by the proviral load and may depend on genetic factors, however, it is not well understood why some HTLV-1 infected people develop the disease while others do not. The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals. Methods: Blood samples were collected from 10 individuals, and DNA was extracted from PBMCs to measure the HTLV-1 proviral load. The gp46 coding sequences were amplified PCR, cloned and sequenced. The molecular characterization was performed using bioinformatics tools. Results: The median HTLV-1 proviral load of HC (n = 5) and HAM/TSP (n = 5) patients was similar (average 316,227 copies/106 PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. Five frequent mutations were detected among groups (HAM/TSP and HC clone sequences). A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53–75 and 175–209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46. Conclusions: The most common gp46 mutations were not associated clinical status because they were found in only one individual, except for the V247I mutation, that was found at viral clones from HAM/TSP ad HC individuals. Because of this, we cannot associate any of the gp46 found mutations with the clinical profile. Salvador

p. 335–345 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-04-22T16:21:32Z No. of bitstreams: 1 10.4137BBI.S12093.pdf: 1564997 bytes, checksum: f165a32def8564d25b1536d70bad953f (MD5) Approved for entry into archive by Patricia Barroso (pbarroso@ufba.br) on 2014-08-11T19:09:20Z (GMT) No. of bitstreams: 1 10.4137BBI.S12093.pdf: 1564997 bytes, checksum: f165a32def8564d25b1536d70bad953f (MD5) Made available in DSpace on 2014-08-11T19:09:20Z (GMT). No. of bitstreams: 1 10.4137BBI.S12093.pdf: 1564997 bytes, checksum: f165a32def8564d25b1536d70bad953f (MD5) Previous issue date: 2013 The purpose of this study was to investigate the balance between transfer ribonucleic acid (tRNA) supply and demand in retrovirus-infected cells, seeking the best targets for antiretroviral therapy based on the hypothetical tRNA Inhibition Therapy (TRIT). Codon usage and tRNA gene data were retrieved from public databases. Based on logistic principles, a therapeutic score (T-score) was calculated for all sense codons, in each retrovirus-host system. Codons that are critical for viral protein translation, but not as critical for the host, have the highest T-score values. Theoretically, inactivating the cognate tRNA species should imply a severe reduction of the elongation rate during viral mRNA translation. We developed a method to predict tRNA species critical for retroviral protein synthesis. Four of the best TRIT targets in HIV-1 and HIV-2 encode Large Hydrophobic Residues (LHR), which have a central role in protein folding. One of them, codon CUA, is also a TRIT target in both HTLV-1 and HTLV-2. Therefore, a drug designed for inactivating or reducing the cytoplasmatic concentration of tRNA species with anticodon TAG could attenuate significantly both HIV and HTLV protein synthesis rates. Inversely, replacing codons ending in UA by synonymous codons should increase the expression, which is relevant for DNA vaccine design.

Texto completo: acesso restrito. p. 1370-1372 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-04-24T13:48:40Z No. of bitstreams: 1 aid%2E2013%2E0015.pdf: 136604 bytes, checksum: 4fe530a2831063224f021c238edeac3f (MD5) Approved for entry into archive by Patricia Barroso (pbarroso@ufba.br) on 2014-05-01T13:13:06Z (GMT) No. of bitstreams: 1 aid%2E2013%2E0015.pdf: 136604 bytes, checksum: 4fe530a2831063224f021c238edeac3f (MD5) Made available in DSpace on 2014-05-01T13:13:06Z (GMT). No. of bitstreams: 1 aid%2E2013%2E0015.pdf: 136604 bytes, checksum: 4fe530a2831063224f021c238edeac3f (MD5) Previous issue date: 2013 Human T cell leukemia virus type 1 (HTLV-1) is associated with a neurological syndrome named tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) and the disease progression involves viral factors. The gp21 glycoprotein is involved in envelope trafficking and membrane targeting while the bZIP protein is indispensable for cell growth and proliferation. This study aimed to assess the molecular diversity of gp21 and HBZ proteins in TSP/HAM and healthy carriers. DNA samples from HTLV-1-infected individuals were submitted to PCR and sequencing, and the molecular analyses were performed using bioinformatics tools. From eight gp21-analyzed sequences one amino acid change (Y477H) was associated with the switch of a helix to coil structure at secondary structure prediction. From 10 HBZ analyzed sequences, two amino acid changes were identified (S9P and T95I) at the activation domain. One mutation (R112C) located at the nuclear localization signal was present in 66.7% and 25% of healthy carriers (HC) and TSP/HAM groups, respectively. This is the first report of mutations in the HBZ region. These polymorphisms might be important for viral fitness.

p. 1-10 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-06-25T17:58:22Z No. of bitstreams: 1 9999999999999999999ff.pdf: 959098 bytes, checksum: 50b03165d54f8297f87c9e137a48338f (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-26T13:17:19Z (GMT) No. of bitstreams: 1 9999999999999999999ff.pdf: 959098 bytes, checksum: 50b03165d54f8297f87c9e137a48338f (MD5) Made available in DSpace on 2013-11-26T13:17:19Z (GMT). No. of bitstreams: 1 9999999999999999999ff.pdf: 959098 bytes, checksum: 50b03165d54f8297f87c9e137a48338f (MD5) Previous issue date: 2013 Background: Human T-cell Leukemia Virus type 1 (HTLV-1) is the etiological agent of tropical spastic paraparesis/ HTLV-associated myelopathy (HAM/TSP) that can be identified in around 0.25%–3.8% of the infected population. Disease progression can be monitored by the proviral load and may depend on genetic factors, however, it is not well understood why some HTLV-1 infected people develop the disease while others do not. The present study attempts to assess the molecular diversity of gp46 glycoprotein in HAM/TSP patients and Health Carrier (HC) individuals. Methods: Blood samples were collected from 10 individuals, and DNA was extracted from PBMCs to measure the HTLV-1 proviral load. The gp46 coding sequences were amplified PCR, cloned and sequenced. The molecular characterization was performed using bioinformatics tools. Results: The median HTLV-1 proviral load of HC (n = 5) and HAM/TSP (n = 5) patients was similar (average 316,227 copies/106 PBMCs). The gp46 molecular characterization of 146 clones (70 HC and 76 HAM/TSP) revealed an overall diversity, within HC and HAM/TSP clones, of 0.4% and 0.6%, respectively. Five frequent mutations were detected among groups (HAM/TSP and HC clone sequences). A single amino acid (aa) substitution (S35L) was exclusive for the HC group, and three gp46 substitutions (F14S, N42H, G72S) were exclusive for the HAM/TSP group. The remaining frequent mutation (V247I) was present in both groups (p = 0.0014). The in silico protein analysis revealed that the mutated alleles F14S and N42H represent more hydrophilic and flexible protein domains that are likely to be less antigenic. The Receptor Binding Domain is quite variable in the HAM/TSP group. Two other domains (aa 53–75 and 175–209) that contain multiple linear T-cell epitopes showed genetic diversity in both HAM/TSP and HC groups. Further analysis revealed 27 and 13 T-cell epitopes for class I HLA alleles and class II HLA alleles, when analyzing the entire gp46. Conclusions: The most common gp46 mutations were not associated clinical status because they were found in only one individual, except for the V247I mutation, that was found at viral clones from HAM/TSP ad HC individuals. Because of this, we cannot associate any of the gp46 found mutations with the clinical profile. Salvador

Texto completo: acesso restrito. p. 1428–1436 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-07-15T13:06:44Z No. of bitstreams: 1 Liliane Lins.pdf: 123808 bytes, checksum: 5d13c0001a41d53221a8388c058dea62 (MD5) Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-11-14T13:00:06Z (GMT) No. of bitstreams: 1 Liliane Lins.pdf: 123808 bytes, checksum: 5d13c0001a41d53221a8388c058dea62 (MD5) Made available in DSpace on 2014-11-14T13:00:07Z (GMT). No. of bitstreams: 1 Liliane Lins.pdf: 123808 bytes, checksum: 5d13c0001a41d53221a8388c058dea62 (MD5) Previous issue date: 2012 Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been implicated in several disorders, including periodontal disease. The proviral load is an important biological marker for understanding HTLV-1 pathogenesis and elucidating whether or not the virus is related to the clinical manifestation of the disease. This study describes the oral health profile of HTLV-1 carriers and HAM/TSP patients in order to investigate the association between the proviral load in saliva and the severity of the periodontal disease and to examine virus intra-host variations from peripheral blood mononuclear cells and saliva cells. It is a cross-sectional analytical study of 90 individuals carried out from November 2006 to May 2008. Of the patients, 60 were HTLV-1 positive and 30 were negative. Individuals from the HTLV-1 positive and negative groups had similar mean age and social-economic status. Data were analyzed using two available statistical software packages, STATA 8.0 and SPSS 11.0 to conduct frequency analysis. Differences of P

Texto completo: acesso restrito. p. 2066–2072 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-02-18T14:16:33Z No. of bitstreams: 1 Bernardo Galvao Castro.pdf: 175093 bytes, checksum: 7161dacf3400a63091b7578201e1e0d9 (MD5) Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-11-28T15:45:58Z (GMT) No. of bitstreams: 1 Bernardo Galvao Castro.pdf: 175093 bytes, checksum: 7161dacf3400a63091b7578201e1e0d9 (MD5) Made available in DSpace on 2014-11-28T15:45:58Z (GMT). No. of bitstreams: 1 Bernardo Galvao Castro.pdf: 175093 bytes, checksum: 7161dacf3400a63091b7578201e1e0d9 (MD5) Previous issue date: 2011 The extraordinary genetic diversity and immune evasion of human immunodeficiency virus (HIV) pose significant challenges for vaccine development and antiretroviral therapy efficacy. The objective of this study was to characterize the molecular profile of HIV-1 epidemic in Salvador, Bahia, Brazil, determining the genetic subtypes and the presence of antiretroviral resistance mutations. HIV-1 pol DNA sequences from 57 individuals infected with HIV were obtained by PCR, followed by sequencing. The subtypes were determined by phylogenetic analyses and the intersubtype recombination was investigated by bootscanning. The pol subtypes were compared with gag and env subtypes. Antiretroviral susceptibility was evaluated through the Stanford HIV resistance Database. The subtypes frequencies were: 77.2% of subtype B, 1.8% of subtype F1, and 21.0% of BF recombinant forms. Two intergenic and three intragenic BF recombinant patterns were observed. Six (10.5%) viruses were related to CRF28/CRF29, two were related to CRF12 (3.5%), and one (1.8%) was CRF39. Fourteen (24.6%) strains carried one or more mutations associated with at least intermediate resistance: 24.6% had resistance to nucleoside reverse transcriptase inhibitors, 21.0% to non-nucleoside reverse transcriptase inhibitors, and 7% to protease inhibitors. The substitutions I54V (7.0%), M184V (14.0%), and K103N (10.5%) were the most frequent within each class of drugs. The results show a high diversity of BF genotypes and a lower prevalence of major reverse transcriptase and protease drug resistance mutations in Salvador, compared with other regions of Brazil. These findings may contribute to improve treatment strategies of patients infected with HIV-1 from this Brazilian region.

Texto completo: acesso restrito. p.1249-1254 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-07-12T13:39:26Z No. of bitstreams: 1 aid%2E2010%2E0068.pdf: 1878328 bytes, checksum: c8905a23e5212aeaabc9ce9b8f103d4c (MD5) Approved for entry into archive by Flávia Ferreira(flaviaccf@yahoo.com.br) on 2013-07-30T15:01:45Z (GMT) No. of bitstreams: 1 aid%2E2010%2E0068.pdf: 1878328 bytes, checksum: c8905a23e5212aeaabc9ce9b8f103d4c (MD5) Made available in DSpace on 2013-07-30T15:01:45Z (GMT). No. of bitstreams: 1 aid%2E2010%2E0068.pdf: 1878328 bytes, checksum: c8905a23e5212aeaabc9ce9b8f103d4c (MD5) Previous issue date: 2010 Besides being extremely useful in measuring the level of HIV-1 diversity and prevalence in populations, the molecular analysis of genomic sequences provides crucial surveillance support and aids in the development of new therapies and effective vaccines. The present study focused on gag and env DNA and amino acid sequences that were generated from samples taken from 61 infected patients in the City of Salvador, Bahia, located in northeastern Brazil. In order to determine selective pressure and predict coreceptor usage, Bioinformatics tools were employed in phylogeny reconstruction. Fifty-six (91.8%) viruses were classified as belonging to subtype B, three (4.9%) from F1, and two (3.3%) from BF1 recombinants. Based on the characterization of the V3 region, the subtype B strains were represented by eight (18.2%) Brazilian variants (B’-GWGR), 20 (46.5%) European/EUA B variants (GPGR), and 15 (34.9%) GXGX variants. The mean time elapsed since diagnosis was 13 years among subtype B’ and 9 years in subtype B. The mean dN/dS ratios from the GWGR, GPGR, and GXGX groups, when compared to an HXB2 reference, were 0.72, 0.77, and 0.67, respectively. Seventy-six percent of the viruses studied were predicted to use the CCR5 coreceptor for cell entry (R5 viruses), while 24% were predicted to use the CXCR4 or were classified as dual tropic viruses. The prevalence of subtypes B' and recombinant B/F1 was shown to be lower than findings from previous studies performed both in Brazil (B’) and in Bahia (B/F1). The association between subtype B’ and a lengthy period of time since diagnosis can be correlated with a slower disease progression in infected patients, when compared with those infected with subtype B.

Texto completo: acesso restrito. p. 391–399 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-10-29T16:08:18Z No. of bitstreams: 1 21414_ftp.pdf: 269246 bytes, checksum: 37ce18cd263f9f02f477c37f23d310ec (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-18T20:52:34Z (GMT) No. of bitstreams: 1 21414_ftp.pdf: 269246 bytes, checksum: 37ce18cd263f9f02f477c37f23d310ec (MD5) Made available in DSpace on 2013-11-18T20:52:34Z (GMT). No. of bitstreams: 1 21414_ftp.pdf: 269246 bytes, checksum: 37ce18cd263f9f02f477c37f23d310ec (MD5) Previous issue date: 2009 The HIV-1 genetic variability in Bahia state, Brazil, was investigated. DNA samples from 229 and 213 HIV-1-infected individuals were analyzed using the heteroduplex mobility assay (HMA) in gag and env fragments, respectively. One hundred seventy-five samples were characterized in both genes. Thirty-two subtype F and BF recombinant viruses were sequenced and analyzed by phylogenetic methods. The combination of HMA and sequencing results showed that seven different HIV-1 genotypes comprised this sample: 147 (84%) B/B, 4 (2.3%) F/F, 3 (1.7%) B/F, 1 (0.6%) F/B, 1 (0.6%) F/D, 1 (0.6%) BF/F, and 18 (10.3%) BF/B. A significant divergence was observed between these two techniques results (84.4%). This is explained by the low accuracy of the HMA for detecting recombinant viruses. These recombinants were unrelated to CRF12, while two sequences were related to CRF28 and CRF29. Nineteen BF mosaics shared the same gag breakpoint. In conclusion, the use of HMA may be inappropriate in regions where different subtypes are co-circulating. Subtype B is the most common genotype, however, an increased prevalence (13.1%) of different BF variants and a potentially new CRF suggest that recombination is occurring frequently in Bahia. These viruses were associated with women infected heterosexually. Finally, this study identified the presence of an F/D recombinant HIV-1 in Brazil.

Texto completo: acesso restrito. p. 1966-1971 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2013-11-07T13:41:49Z No. of bitstreams: 1 21300_ftp.pdf: 115572 bytes, checksum: 4e50eac27e29a127aa4ac829645eb933 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-11-08T18:34:24Z (GMT) No. of bitstreams: 1 21300_ftp.pdf: 115572 bytes, checksum: 4e50eac27e29a127aa4ac829645eb933 (MD5) Made available in DSpace on 2013-11-08T18:34:24Z (GMT). No. of bitstreams: 1 21300_ftp.pdf: 115572 bytes, checksum: 4e50eac27e29a127aa4ac829645eb933 (MD5) Previous issue date: 2009 To determine the seroprevalence of HTLV-1 in Brazil, and to review the virus molecular epidemiology in this Amazon population (Rio Branco-Acre), 219 blood donors were screened for HTLV-1. Only one case of infection (0.46% seroprevalence) was detected during July 2004 screening at the Acre Hospital Foundation (FUNDACRE). Neighbor-joining and Maximum Likelihood phylogenetic analyses of two (n = 2) complete LTR region sequences were performed with the PAUP* software. Since the HTLV-1 envelope surface (gp46) and transmembrane (gp21) glycoproteins are important for virus fitness, three envelope glycoproteins sequences (n = 3) were analyzed using the Prosite tool to determinate potential protein sites. Phylogenetic analysis demonstrated that the new isolate described in this study, and the unpublished LTR strain described in a previous report belong to the Transcontinental subgroup of the Cosmopolitan subtype, inside the Latin American cluster. A similar result was obtained when submitting, to the Automated Genotyping System, three LTR partial sequences from a previous study of the seroprevalence of HTLV-1 in the same Amazon population. In all analyzed env sequences, the potential protein site was found: two PKC phosphorylation sites at amino acid (aa) positions 310–312 and 342–344, one CK2 phosphorylation site at 194–197aa, three N-glycosylation sites at 222–225aa, 244–247aa and 272–275aa, and a single N-myristylation site at 327–338aa. In conclusion, potential protein sites described in HTLV-1 gp46 and gp21 confirm the presence of conserved sites in the HTLV-1 envelope proteins, likewise phylogenetic analysis suggests a possible recent introduction of the virus into North Brazil.

Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2011-10-07T16:35:32Z No. of bitstreams: 1 eeeee.pdf: 47492 bytes, checksum: bb2b8ed4d2bf13b9a47f2499eb1ed3be (MD5) Made available in DSpace on 2011-10-07T16:35:32Z (GMT). No. of bitstreams: 1 eeeee.pdf: 47492 bytes, checksum: bb2b8ed4d2bf13b9a47f2499eb1ed3be (MD5) Previous issue date: 2006 Previous data suggest that Salvador, the capital of the State of Bahia, a northeastern state of Brazil, has the highest prevalence of HTLV infection in blood donors among Brazilian cities. The aim of this case-control study was to identify the determinants of risk for HTLV infection among blood donors in the city of Salvador. Between January 2000 and December 2003, 504 blood donors with positive screening tests for HTLV infection (unconfirmed prevalence of 0.48%) were invited to participate in our study. A total of 154 had performed a Western Blot (WB) test, 139 were of which found to be positive (false positive screening rate 9.9%). Using a standardized questionnaire, a single interviewer obtained information on demographic, socio-economical and educational characteristics, as well as sexual behavior from 91 out of the 139 positive by WB and from 194 HTLV-negative blood donors. Prevalence of HTLV infection was 0.48%. Multivariate analysis revealed women (OR 3.79 [1.61-8.88], p=0.002), low family income* (OR 3.37 [1.17-9.66], p=0.02), self-reported history of sexual transmitted diseases (OR 6.15 [2.04-18.51], p=0.001), 2 or more sexual partners during life (OR 9.29 [2.16-39.94], p=0.0020) and inconsistent use of condoms (OR 4.73 [1.98-11.26], p=0.0004) as risk factors for HTLV infection. In accordance with previous published data, our results point to an association between low socio-economical level, poor education and unsafe sexual behavior with HTLV infection. We observed a lower prevalence of HLTV infection when compared to São José do Rio Preto

Para cada doador de sangue soropositivo (ELISA, Abbott®) para HTLV-I/II, de dezembro de 1998 a março de 2001, também foram selecionados dois soronegativos. As amostras séricas foram re-testadas pelo ELISA (Murex®) e aquelas que permaneceram soropositivas foram testadas pelo Western Blot e pela PCR. Das 11.121 amostras séricas, 73 (0,66%) foram positivas (Abbott®), mas somente 12 (0,11%) permaneceram positivas (Murex®), enquanto que as 146 soronegativas foram confirmadas, apesar de ser sofrível o índice de concordância entre os dois ELISA. O Western Blot confirmou as 12 amostras como soropositivas: 8 (0,07%) HTLV-I; duas (0,02%) HTLV-II e duas (0,02%) indeterminadas - sendo pela PCR uma pelo HTLV-I e a outra pelo HTLV-II. Em conclusão, nessa população da Amazônia Ocidental foi muito baixa a soroprevalência de HTLV-I/II, apesar de ser esperada maior prevalência do HTLV-II devido a grande miscigenação racial indígena. Between December 1998 and March 2001, for each HTLV-I/II seropositive blood donor (ELISA, Abbott®), two HTLV-I/II seronegative blood donors were also chosen. The blood samples were re-tested by ELISA (Murex®), and those seropositives were also tested by western blot and PCR. Of the 11,121 blood samples, 73 (0.66%) were positives (Abbott®), but only 12 (0.11%) remained positives (Murex®), whereas the 146 seronegatives were confirmed, even though the concordance index between these two ELISA tests was hopeless. The Western Blot confirmed the twelve blood samples as seropositives: 8 (0.07%) HTLV-I; two (0.02%) HTLV-II and two (0.02%) indeterminate, being by PCR, one HTLV-I and the other HTLV-II. Concluding, in this Western Amazon population the HTLV-I/II seroprevalence was too low, in spite of the greater prevalence of HTLV-II expected due to a great indigenous racial mixture.

Texto completo: acesso restrito. p. 527-531 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2013-12-09T14:32:06Z No. of bitstreams: 1 Inês Dourado.pdf: 259790 bytes, checksum: 586698e797be87ba92680eaa56fbbace (MD5) Made available in DSpace on 2013-12-09T14:32:06Z (GMT). No. of bitstreams: 1 Inês Dourado.pdf: 259790 bytes, checksum: 586698e797be87ba92680eaa56fbbace (MD5) Previous issue date: 2003 The city of Salvador has the highest prevalence of HTLV-I among blood donors in Brazil. To study the prevalence of HTLV-I among the general population of Salvador, 30 “sentinel surveillance areas” were selected for the investigation of various infectious diseases, and 1385 individuals within these areas were surveyed according to a simple random sample procedure. ELISA was used to screen plasma samples for antibodies to HTLV-I, and the positive samples were tested by a confirmatory assay (Western blotting). The overall prevalence of HTLV-I was 1.76% (23/1385). Infection rates were 1.2% for males and 2.0% for females. Specific prevalence demonstrated an increasing linear trend with age. No one younger than 13 years of age was infected. Multivariate analysis estimated adjusted odds ratios for the association of HTLV-I with age of 9.7 (3.3; 30.4) for females and 12.3 (1.47; 103.1) for males. Less education and income might be associated with HTLV-I infection in females. Phylogenetic analysis of the long terminal repeat fragments showed that most of the samples belonged to the Latin American cluster of the Transcontinental subgroup (Cosmopolitan subtype). For the entire city of Salvador, it is estimated that ~40,000 individuals are infected with HTLV-I. Our results suggest multiple post-Colombian introductions of African HTLV-Ia strains in Salvador.

p. 677-683,Nov-Dez. Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2011-09-09T18:45:28Z No. of bitstreams: 1 20298.pdf: 97854 bytes, checksum: 8a8ed086eb73c2df172c8d76d02d791a (MD5) Made available in DSpace on 2011-09-09T18:45:29Z (GMT). No. of bitstreams: 1 20298.pdf: 97854 bytes, checksum: 8a8ed086eb73c2df172c8d76d02d791a (MD5) Previous issue date: 2003 Para cada doador de sangue soropositivo (ELISA, Abbott®) para HTLV-I/II, de dezembro de 1998 a março de 2001, também foram selecionados dois soronegativos. As amostras séricas foram re-testadas pelo ELISA (Murex®) e aquelas que permaneceram soropositivas foram testadas pelo Western Blot e pela PCR. Das 11.121 amostras séricas, 73 (0,66%) foram positivas (Abbott®), mas somente 12 (0,11%) permaneceram positivas (Murex®), enquanto que as 146 soronegativas foram confirmadas, apesar de ser sofrível o índice de concordância entre os dois ELISA. O Western Blot confirmou as 12 amostras como soropositivas: 8 (0,07%) HTLV-I; duas (0,02%) HTLV-II e duas (0,02%) indeterminadas – sendo pela PCR uma pelo HTLV-I e a outra pelo HTLV-II. Em conclusão, nessa população da Amazônia Ocidental foi muito baixa a soroprevalência de HTLV-I/II, apesar de ser esperada maior prevalência do HTLV-II devido a grande miscigenação racial indígena. Uberaba

Texto completo: acesso restrito. p. 536-542 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2013-12-16T14:25:31Z No. of bitstreams: 1 Alcantara Jr., L.C..pdf: 4754821 bytes, checksum: 3db17ce104d62660d53fa3a93f69e4e1 (MD5) Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-11-24T15:30:48Z (GMT) No. of bitstreams: 1 Alcantara Jr., L.C..pdf: 4754821 bytes, checksum: 3db17ce104d62660d53fa3a93f69e4e1 (MD5) Made available in DSpace on 2014-11-24T15:30:48Z (GMT). No. of bitstreams: 1 Alcantara Jr., L.C..pdf: 4754821 bytes, checksum: 3db17ce104d62660d53fa3a93f69e4e1 (MD5) Previous issue date: 2003 The city of Salvador, Bahia, Brazil, has sociodemographic characteristics similar to some African cities. Up to now, it has had the highest prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection (1.74%) in the country. To investigate which strains of HTLV-I are circulating in Salvador, we studied isolates from 82 patients infected with HTLV-I: 19 from the general population, 21 from pregnant women, 16 from intravenous drug users, and 26 from patients and their family attending a neurologic clinic. Phylogenetic analysis from part of the LTR fragments showed that most of these isolates belonged to the Transcontinental subgroup of the Cosmopolitan subtype (HTLV-Ia). Only one sample from a pregnant woman was closely related to the Japanese subgroup, suggesting recent introduction of a Japanese HTLV-I lineage into Salvador. βA-Globin haplotypes were examined in 34 infected individuals and found to be atypical, confirming the racial heterogeneity of this population. A total of 20 chromosomes were characterized as Central African Republic (CAR) haplotype (29.4%), 31 (45.6%) were characterized as Benin (BEN) haplotype, and 17 (25%) were characterized as Senegal (SEN) haplotype. Five patients' genotypes (14.7%) were CAR/CAR; 10 (29,4%), BEN/BEN; 9 (26.5%), CAR/BEN; 2 (5.9%), BEN/SEN; and 7 (20.6%), SEN/SEN. One patient's genotype (2.9%) was CAR/SEN. The βA-globin haplotype distribution in Salvador is unusual compared with other Brazilian states. Our data support the hypothesis of multiple post-Columbian introductions of African HTLV-Ia strains in Salvador, Bahia, Brazil.

Texto completo: acesso restrito. p. 503–507 Submitted by Suelen Reis (suelen_suzane@hotmail.com) on 2012-12-19T17:29:27Z No. of bitstreams: 1 j.1365-3024.2001.00407.pdf: 95167 bytes, checksum: 5466c786d6eeb307e0761d660b77ce00 (MD5) Made available in DSpace on 2012-12-19T17:29:27Z (GMT). No. of bitstreams: 1 j.1365-3024.2001.00407.pdf: 95167 bytes, checksum: 5466c786d6eeb307e0761d660b77ce00 (MD5) Previous issue date: 2001 Eosinophils, immunoglobilin (Ig)E and cytokines have important roles in defence mechanisms against helminths. In this study, the influence of HTLV-1 infection, characterized by a Th1 type of immune response, was evaluated on the cytokine pattern and parasitic specific IgE response in patients with strongyloidiasis. Patients were divided into four groups: strongyloidiasis without HTLV-1 infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and controls without either helminth infection or HTLV-1. The cytokine profile was determined in supernatants of mononuclear cells stimulated with Strongyloides stercoralis crude antigen and the parasite specific IgE was measured by ELISA. Patients coinfected with HTLV-1 had higher levels of interfron (IFN)-γ and interleukin (IL)-10 (P < 0·05) and lower levels of IL-5 and IgE (P < 0·05) than patients with strongyloidiasis without HTLV-1. There was an inverse relationship between IFN-γ and IL-5 (P = 0·01; rs = − 0·37) and between IFN-γ and parasite specific IgE (P = 0·01; rs = − 0·39), and a direct relationship between IFN-γ and IL-10 (P = 0·04; rs = 0·35). These data show that coinfection with HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis consistent with a relative switch from Th2 to Th1 response. Immunological responses such as these are important in the control of this helminthic infection.

Orientadores: Clarice Weis Arns, Márcia Bianchi dos Santos Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: A evolução e a dinâmica populacional dos Coronavírus (CoVs) ainda permanecem pouco exploradas. No presente estudo, análises filogenéticas e de filogeografia foram conduzidas para investigar a dinâmica evolutiva dos CoVs detectados em aves silvestres e sinantrópicas. Um total de 500 amostras, que inclui os suabes traqueais e cloacais coletados de 312 aves silvestres pertencentes a 42 espécies, foram analisadas através da RT-qPCR. Sessenta e cinco amostras (13%) provenientes de 23 espécies foram positivas para o Coronavírus aviário (AvCoV). Trezentos e duas amostras foram investigadas para a pesquisa do Pan-Coronavírus (Pan-CoV) através do nPCR, destas, 17 (5,6%) foram positivas, sendo que 11 foram detectadas em espécies diferentes. Análises filogenéticas dos AvCoVs revelaram que as sequências de DNA das amostras coletadas no Brasil não agruparam com nenhuma das sequências do gene Spike (S1) dos AvCoVs depositados no banco de dados GenBank. Análise Bayesiana estimou uma variante do AvCoV proveniente da Suécia (1999) como o ancestral comum mais recente dos AvCoVs detectados neste estudo. Além disso, as análises realizadas através do "Bayesian Skyline Plot" (BSP) inferiram um aumento na dinâmica da população demográfica do AvCoV em diferentes espécies de aves silvestres e sinantrópicas. As análises filogenéticas do Pan-CoV mostrou que a maioria das amostras se agruparam com o Vírus da Hepatite Murina A59 (MHV A59), CoV pertencente ao grupo dos Beta-CoVs. Uma amostra [CoV detectado em Amazona vinacea(Papagaio-de-peito-roxo)] se agrupou com um CoV de Suínos, o PCoV HKU15, que pertence ao gênero Delta-CoV, ainda não relatado na América do Sul. Nossos achados sugerem que as aves podem ser novos potenciais hospedeiros responsáveis pela propagação e disseminação de diferentes CoVs para diferentes espécies de animais Abstract: The evolution and population dynamics of Coronaviruses (CoVs) still remain underexplored. In the present study, phylogenetic and phylogeographic analyseswere conducted to investigate the evolutionary dynamics of CoV detected in wild and synanthropic birds. A total of 500 samples, including tracheal and cloacal swabs collected from 312 wild birds belonging to 42species, were analysed by RT-qPCR. A total of 65 samples from 23bird species were positive for Avian Coronaviruses (AvCoVs).Three hundred and two samples were screened for the Pan-Coronavirus (Pan-CoV) through the nPCR, 17 (5.6%) were positive, being that 11 were detected in different species. AvCoVs phylogenetic analyses revealed that the DNA sequences from samples collected in Brazil did not cluster with any of the AvCoV S1 gene sequences deposited in the GenBank database. Bayesian framework analysis estimated an AvCoV strain from Sweden (1999) as the most recent common ancestor of the AvCoVs detected in this study. Furthermore, Bayesian Skyline Plot (BSP) analysis inferred an increase in the AvCoV dynamic demographic population in different wild and synanthropic bird species. Phylogenetic analysis of the Pan-CoV showed that most of the samples clustered with the Murine Hepatitis Virus A59 strain (MHV A59) belong to the BetaCoV group. Besides, one of our samples [CoV detected in Amazona vinacea (parrot-breasted-purple)] clustered with a CoV isolated from pigs, PCoV HKU15, belonging to the DeltaCoV genus, still not reported in South America. Our findings suggest that birds may be potential new hosts responsible for spreading of different CoVs for different species of animals Doutorado Microbiologia Doutor em Genética e Biologia Molecular

Submitted by Pos-Graduação Medicina e Saúde (ppgms@ufba.br) on 2017-08-25T18:12:43Z No. of bitstreams: 1 Sara Nunes Vaz_ Dissertação de Mestrado.pdf: 3195937 bytes, checksum: 02346392f9fca991003229c3f810b525 (MD5) Approved for entry into archive by Edvaldo Souza (edvaldosouza@ufba.br) on 2017-09-18T18:53:03Z (GMT) No. of bitstreams: 1 Sara Nunes Vaz_ Dissertação de Mestrado.pdf: 3195937 bytes, checksum: 02346392f9fca991003229c3f810b525 (MD5) Made available in DSpace on 2017-09-18T18:53:03Z (GMT). No. of bitstreams: 1 Sara Nunes Vaz_ Dissertação de Mestrado.pdf: 3195937 bytes, checksum: 02346392f9fca991003229c3f810b525 (MD5) RESUMO NA LÍNGUA VERNÁCULA Introdução: Cerca de 35,3 milhões de pessoas em todo o mundo estão infectadas com o Vírus da Imunodeficiência Humana (HIV) e destas, 2,7 milhões são crianças com menos de 15 anos de idade. A transmissão vertical (TV) do HIV-1 é responsável por 90% de todas as infecções em crianças, podendo ocorrer durante a gravidez, no momento do parto e através do leite materno. Apesar das grandes conquistas na prevenção da TV no Brasil, crianças ainda vêm sendo infectadas. Objetivo: Avaliar a diversidade genética do vírus HIV-1 em crianças/ adolescentes infectados por via vertical em comparação ao vírus materno. Materiais e métodos: Amostras de sangue total de 41 sujeitos infectados pelo HIV-1 (22 crianças e 19 mães) foram coletadas. DNA genômico foi extraído e fragmentos de gag, pol e env amplificados através de PCR e sequenciados. Reconstruções filogenéticas foram utilizadas para subtipar as sequências e identificar recombinantes. Sequências de aminoácidos dos pares de mães e filhos virgens de terapia antirretroviral (TARV) foram analisadas quanto ao número de mutações não sinônimas. A região da alça V3 das sequências de env foram analisadas para identificação de assinaturas e predição in silico do coreceptor viral. Mutações de resistência associadas aos inibidores de protease, transcriptase reversa e fusão foram identificadas nas sequências de pol e env. Resultados: A prevalência de subtipo B puro nesta população foi de 82,1% e de recombinantes BF 17,9%. A maior frequência de mutação não sinônima foi encontrada em Env (9.9%), seguida de Gag (2.7%) e Pol (1.9%). Análises na alça V3 da região do envelope revelaram 19,5% de subtipo B’ (GWGR); 46,4% de B (GPGR) e 34,1% de outras variantes (GXPX). Com relação à predição de coreceptor, 46,3% das sequências eram de vírus X4 (CXCR4) e destas, dez (52,6%) eram sequências de mães. Uma prevalência de 43,9% de mutações associadas às drogas antirretrovirais (DRAM) nas sequências de pol foi identificada. Dentre as crianças/adolescentes virgens de tratamento, 33,3% apresentaram pelo menos uma mutação associada aos inibidores de protease e/ou transcriptase reversa. Mutações de resistência transmitida (tDRM) foram detectadas numa prevalência de 4,9%. Encontramos uma baixa prevalência de mutações no gene env, associadas à resistência ao inibidor de fusão: 4,9% de HR1 e 14,6% de HR2. Conclusões: Os resultados ressaltam a importância de testar as gestantes e mantê-las em TARV para supressão do vírus, evitando assim a TV. Para dar melhor suporte às políticas públicas de saúde na eliminação da TV do HIV-1 e na seleção de regimes de TARV ativa para mães e bebês, é essencial entender a epidemiologia molecular do vírus. Palavras-chaves: HIV-1; transmissão vertical; diversidade genética. RESUMO EM LÍNGUA ESTRANGEIRA Introduction: Around 35.3 million people worldwide are infected with Human Immunodeficiency Virus (HIV) around 2.7 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all HIV-1 infections in children and can occur during pregnancy, delivery and through breast-feeding. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Objective: Characterize the genetic diversity of HIV-1 isolates in infected children by the vertical route in relation to the maternal virus, in a population from Salvador, the capital of Bahia State, Brazil. Methods: Samples from 41 HIV-1 infected individuals from 19 families were collected. Genomic DNA was extracted; fragments from gag, pol and env were amplified and sequenced directly. Phylogenetic reconstruction was performed to subtype the sequences and find recombinants. The V3 loop from env sequences was analyzed and coreceptor usage was predicted. Drug resistance analyses were performed in pol and env sequences. Results: We found 82.1% of subtype B and 17.9% of BF recombinants. The highest frequency of non-synonymous mutations was found in Env (9.9%), followed by Gag (2.7%) and Pol (1.9%). Based on V3 characterization, 8 (19.5%) Brazilian B’ (GWGR), 19 (46.4%) European/ EUA B (GPGR) and 14 (34.1%) GXGX variants were found. With regard to coreceptor usage, 19 (46.3%) V3 sequences were predicted to use the CXCR4 coreceptor (X4 virus) and 10 (52.6%) of them were mothers. A prevalence of 43.9% drug resistance-associated mutations in the pol sequences was identified. 33.3% of the drug-naïve children/adolescents presented at least 1 mutation related to PI/NRTI/NNRTI resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On the env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations. Conclusion: This study thus highlights the importance of increasing antenatal testing and maintaining mothers on suppressed ART. To better support public health policies to eliminate MTCT and select active regimens for mothers and babies, it is essential to understand the molecular epidemiology of the virus. Key-words: HIV-1; mother-to-child-transmission; viral diversity.

determinar os fatores de risco associados à infecção pelo HTLV em doadores de sangue do Estado da Bahia e caracterizar genotipicamente os isolados virais. Desenho do Estudo: Caso-controle. Material e métodos: 504 doadores com teste sorológico de triagem positivo (total de doações = 104.835, prevalência não confirmada de 0,48%) foram convidados por carta (X 2) e contato telefônico. 154 (33,1%) compareceram para o teste confirmatório (Western Blot [WB]), dos quais 139 foram positivos (91,9%). 99 dos 139 consentiram em participar do estudo (casos). 194 doadores com teste sorológico de triagem negativo participaram como controles. Foram obtidas informações de ordem demográfica, socioeconômica, educacional e relativas ao comportamento sexual através de um questionário padronizado aplicado por um único entrevistador. Isolados virais de 23 doadores foram sequenciados e analisados filogeneticamente. Resultados: A análise multivariada revelou que sexo feminino (OR=3,8), baixa renda familiar (OR=3,4), DST prévia (OR=6,1), uso inconstante de preservativo (OR=4,7) e número de parceiros durante a vida (OR=9,3) são fatores de risco independentes para infecção pelo HTLV-1. Observamos diferenças significativas de comportamento sexual entre homens e mulheres. Todos os isolados virais analisados pertenceram ao subgrupo transcontinental, subgrupo cosmopolita. Pela primeira vez foi observado um isolado da África do Sul inserido no grupamento latino-americano principal. Conclusão: Os fatores de risco identificados confirmam achados prévios de outros estudos. Os nossos achados sugerem que a principal via de transmissão de HTLV-1 na Bahia seja a sexual, e que as mulheres estão em uma posição de vulnerabilidade. A análise filogenética demonstrou que a África do Sul pode ter contribuído na introdução do HTLV-1 no Brasil. Observamos uma importante queda na prevalência da infecção pelo HTLV-1 em doadores de sangue no nosso Estado na última década.