19 research outputs found

    Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus

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    Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013‚Äď2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain‚ÄďBarr√© syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV

    Estudo in silico para a utilização do HTLV-2 atenuado como vetor vacinal contra a infecção pelo HTLV-1

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    Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2013-10-14T17:28:38Z No. of bitstreams: 1 Fernanda Khouri. Estudo in silico....pdf: 3863859 bytes, checksum: 34a7b6c0bc315b65207169652027de26 (MD5)Made available in DSpace on 2013-10-14T17:28:38Z (GMT). No. of bitstreams: 1 Fernanda Khouri. Estudo in silico....pdf: 3863859 bytes, checksum: 34a7b6c0bc315b65207169652027de26 (MD5) Previous issue date: 2013Funda√ß√£o Oswaldo Cruz. Centro de Pesquisas Gon√ßalo Moniz. Salvador, BA, BrasilO HTLV-1 foi o primeiro retrov√≠rus descrito associado a doen√ßas humanas, tais como leucemia de c√©lula T do adulto (ATLL), paraparesia esp√°stica tropical/mielopatia associada ao HTLV (TSP/HAM), dermatite infecciosa, entre outras. Esse retrov√≠rus possui um genoma de RNA de fita simples, com os genes gag (grupo antig√™nico), env (envelope), pol (polimerase), e uma regi√£o pr√≥xima √† extremidade 3' conhecida como pX. Em cada extremidade do genoma existem sequ√™ncias de repeti√ß√Ķes terminais longas (LTR ‚Äď long terminal repeat), que s√£o essenciais na integra√ß√£o do DNA proviral ao DNA do hospedeiro, e tamb√©m para a regula√ß√£o transcricional do genoma do v√≠rus. Estima-se que cerca de 5-10 milh√Ķes de pessoas estejam infectadas pelo HTLV-1 no mundo. No Brasil, presume-se que 2,5 milh√Ķes de pessoas estejam infectadas. Apesar da infec√ß√£o pelo HTLV-1 ser end√™mica em diferentes regi√Ķes geogr√°ficas do mundo, ainda permanece sem um m√©todo de profilaxia eficaz. Pesquisas realizadas em macacos-esquilos no Instituto Pasteur da Fran√ßa e no Instituto Nacional do C√Ęncer nos EUA avaliaram a imunogenicidade e a efic√°cia de uma vacina contendo o gene env ou env e gag do HTLV-1. Ap√≥s a vacina√ß√£o e transfus√£o de c√©lulas infectadas com o HTLV-1 todos os animais mostraram-se protegidos. Anteriormente a este estudo, pesquisadores do Instituto Nacional do C√Ęncer, NIH-EUA, avaliaram a efic√°cia de um vetor vacinal derivado do v√≠rus da var√≠ola atenuado contendo o gene env do HTLV-1 (R-ALVAC), e ap√≥s o desafio vacinal todos os animais mostraram-se protegidos. Por√©m, a prote√ß√£o destes dois estudos n√£o foi permanente. Entretanto, esses resultados sugerem que uma vacina anti-HTLV-1 pode ser vi√°vel e, acreditamos que a produ√ß√£o dessa vacina tendo como vetor um v√≠rus persistente como o HTLV-2 pode proteger contra a infec√ß√£o pelo HTLV-1. Assim, desenvolvemos em colabora√ß√£o com o NIH, um vetor vacinal contendo as duas regi√Ķes LTR do HTLV-2, para serem inseridos os genes gag e env do HTLV-1 sob o controle da regi√£o 3‚ÄôLTR deste vetor. Para a utiliza√ß√£o desse vetor recombinante faz-se necess√°rio caracterizar a regi√£o promotora do HTLV-2, avaliando assinaturas nucleot√≠dicas presentes em diferentes subtipos, bem como a presen√ßa de motifs importantes para a express√£o do vetor vacinal. Pelo exposto, o objetivo principal desse trabalho foi avaliar in silico a habilidade do vetor recombinante do HTLV-2 poder ser utilizado como vetor vacinal anti-HTLV-1. Nossos resultados revelaram que existem pequenas diferen√ßas na regi√£o promotora dos subtipos HTLV-2a, HTLV-2b, HTLV-2c e HTLV-2d. Algumas altera√ß√Ķes resultam em ganho ou perda de motifs importante para a regula√ß√£o da transcri√ß√£o g√™nica, como o motif E Box, presente nas sequ√™ncias dos diferentes subtipos do HTLV-2 e ausente na regi√£o promotora do vetor. Entretanto, estudos sugerem que esse motif pode ser respons√°vel pela repress√£o da transcri√ß√£o g√™nica e, portanto, essa diferen√ßa encontrada entre o vetor recombinante do HTLV-2 e as diferentes sequ√™ncias analisadas sugere que a transcri√ß√£o g√™nica do vetor vacinal sem esse motif pode ser mais eficiente. Logo, o vetor recombinante do HTLV-2 pode ser utilizado como vetor vacinal anti-HTLV-1 em ensaios pr√©-cl√≠nicos.The HTLV-1 was first described retroviruses associated with human diseases, such as leukemia adult T cell (ATLL), tropical spastic paraparesis / HTLV-associated myelopathy (TSP / HAM), infective dermatitis, among others. This retrovirus has a genome of single-stranded RNA, with the genes gag (group antigen), env (envelope), pol (polymerase), and a region near the 3 'end known as pX. At each end of the genome are sequences of long terminal repeat (LTR) that are essential for the integration of the proviral DNA in the host DNA and also for the transcriptional regulation of the virus genome. It is estimated that about 5-10 million people are infected with HTLV-1 worldwide. In Brazil, it is assumed that 2.5 million people are infected. Despite the HTLV-1 is endemic in different geographic regions of the world still remains without an effective method of prophylaxis. Research conducted in squirrel monkeys at the Pasteur Institute in France and the National Cancer Institute in the USA evaluated the immunogenicity and efficacy of a vaccine containing the env gene or env and gag of HTLV-1. After vaccination and transfusion of infected cells with HTLV-1 all animals were shown to be protected. Prior to this study, researchers from the National Cancer Institute, NIH, USA, evaluated the efficacy of a vector vaccine derived from attenuated smallpox virus containing the env gene of HTLV-1 (R-ALVAC) and after challenge all animals were shown to be protected. However, the protection of these two studies was not permanent. At the same time, these results suggest that a vaccine anti-HTLV-1 may be feasible and we believe that the production of this vaccine as a vector having one persistent virus as HTLV-2 can protect against HTLV-1 infection. Thus, we developed in collaboration with the NIH, a vector vaccine containing the two LTR of HTLV-2, that will be inserted the env and gag genes of HTLV-1. To use this recombinant vector is necessary characterize the promoter region of HTLV-2, evaluating nucleotide signatures present in different subtypes, as well as the presence of motifs important for the expression vector vaccine. For these reasons, the aim of this study was to evaluate in silico the ability of recombinant vector of HTLV-2 be able to be used as a vector vaccine anti-HTLV-1. Our results reveal that there are small differences in the promoter region of HTLV-2a, HTLV-2b, HTLV-2c and HTLV-2d. Some changes results in loss or gain of motifs important for regulation of gene transcription, such as the E box motif present in the sequences of the different subtypes of HTLV-2 and absent in the promoter region of the vector. However, studies suggest that this motif can be responsible for the repression of gene transcription, and therefore this difference found between the recombinant vector of HTLV-2 and different sequences suggested that the analyzed gene transcription vector vaccine without this motif can be more efficient . Therefore, the recombinant vector HTLV-2 can be used in preclinical trials as a vaccine vector for HTLV- 1

    Inferences about the global scenario of human T-cell lymphotropic virus type 1 infection using data mining of viral sequences

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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 ‚Äúa‚ÄĚ. 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
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