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1.
Nat Commun ; 12(1): 4996, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404793

RESUMO

Between 10 and 20 million people worldwide are infected with the human T-cell lymphotropic virus type 1 (HTLV-1). Despite causing life-threatening pathologies there is no therapeutic regimen for this deltaretrovirus. Here, we screened a library of integrase strand transfer inhibitor (INSTI) candidates built around several chemical scaffolds to determine their effectiveness in limiting HTLV-1 infection. Naphthyridines with substituents in position 6 emerged as the most potent compounds against HTLV-1, with XZ450 having highest efficacy in vitro. Using single-particle cryo-electron microscopy we visualised XZ450 as well as the clinical HIV-1 INSTIs raltegravir and bictegravir bound to the active site of the deltaretroviral intasome. The structures reveal subtle differences in the coordination environment of the Mg2+ ion pair involved in the interaction with the INSTIs. Our results elucidate the binding of INSTIs to the HTLV-1 intasome and support their use for pre-exposure prophylaxis and possibly future treatment of HTLV-1 infection.


Assuntos
Antivirais/química , Antivirais/farmacologia , Microscopia Crioeletrônica , Infecções por HTLV-I/tratamento farmacológico , Vírus Linfotrópico T Tipo 1 Humano/efeitos dos fármacos , Amidas , Domínio Catalítico , Deltaretrovirus , Farmacorresistência Viral/efeitos dos fármacos , Integrase de HIV/efeitos dos fármacos , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Naftiridinas/farmacologia , Piperazinas , Piridonas , Proteínas Recombinantes
2.
Dis Mon ; 67(9): 101170, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33618831

RESUMO

Among all the viral infections, acquired immunodeficiency syndrome (AIDS) is considered as one of the most morbid infections caused by the human immunodeficiency virus (HIV). The prime reason for the pathogenesis is the profound immunosuppression that leads to lethal opportunistic infections (OI), neurological disorders, unexpected malignancies and pathologies of the orofacial region. Patients with OI whose HIV status is unknown have shown a mortality rate higher than those with known HIV status. Among HIV-associated infections, orofacial lesions contribute a major proportion of the OI attributed to the plethora of micro-organisms present in the oral cavity. Apart from serious clinical manifestations, opportunistic infections also lead to significant impairment of quality of life. These lesions not only indicate the HIV infection but also among the clinical manifestations, which often occur early in the course of disease. World Health Organization has also provided policies for treatment/prevention of oral lesions, strengthening the promotion and care of oral health in HIV/AIDS patients. The present review provides comprehensive information about orofacial OI in HIV/AIDS patients and emphasis was also given to the malignancies associated with EB and HTLV virus.


Assuntos
Face/virologia , Infecções por HIV/complicações , Doenças da Boca/etiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Deltaretrovirus , Herpesvirus Humano 4 , Humanos , Boca/virologia , Doenças da Boca/prevenção & controle , Doenças da Boca/virologia , Qualidade de Vida , Viroses/etiologia , Viroses/prevenção & controle , Viroses/virologia
3.
mSphere ; 5(5)2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968009

RESUMO

Bats are the reservoir for a large number of zoonotic viruses, including members of Coronaviridae (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2), Paramyxoviridae (Hendra and Nipah viruses), Rhabdoviridae (rabies virus), and Filoviridae (Ebola virus) as exemplars. Many retroviruses, such as human immunodeficiency virus, are similarly zoonotic; however, only infectious exogenous gammaretroviruses have recently been identified in bats. Here, viral metagenomic sequencing of samples from bats submitted for rabies virus testing, largely due to human exposure, identified a novel, highly divergent exogenous Deltaretrovirus from a big brown bat (Eptesicus fuscus) in South Dakota. The virus sequence, corresponding to Eptesicus fuscus deltaretrovirus (EfDRV), comprised a nearly complete coding region comprised of canonical 5'-gag-pro-pol-env-3' genes with 37% to 51% identity to human T-lymphotropic virus (HTLV), an infectious retrovirus that causes T-cell lymphoma. A putative tax gene with 27% identity to HTLV was located downstream of the pol gene along with a gene harbored in an alternative reading frame which possessed a conserved domain for an Epstein-Barr virus nuclear antigen involved in gene transactivation, suggesting a regulatory function similar to that of the deltaretrovirus rex gene. A TaqMan reverse transcriptase PCR (RT-PCR) targeting the pol gene identified 4/60 (6.7%) bats as positive for EfDRV, which, combined with a search of the E. fuscus genome that failed to identify sequences with homology to EfDRV, suggests that EfDRV is an infectious exogenous virus. As all known members of Deltaretrovirus can cause malignancies and E. fuscus is widely distributed in the Americas, often with a colonial roosting behavior in human dwellings, further studies are needed to investigate potential zoonosis.IMPORTANCE Bats host a large numbers of viruses, many of which are zoonotic. In the United States, the big brown bat (Eptesicus fuscus) is widely distributed and lives in small colonies that roost in cavities, often in human dwellings, leading to frequent human interaction. Viral metagenomic sequencing of samples from an E. fuscus bat submitted for rabies testing identified the first exogenous bat Deltaretrovirus The E. fuscus deltaretrovirus (EfDRV) genome consists of the typical deltaretrovial 5'-gag-pro-pol-env-3' genes along with genes encoding two putative transcriptional transactivator proteins distantly related to the Tax protein of human T-cell lymphotrophic virus and nuclear antigen 3B of Epstein-Barr virus. Searches of the E. fuscus genome sequence failed to identify endogenous EfDRV. RT-PCR targeting the EfDRV pol gene identified 4/60 (6.7%) bats with positive results. Together, these results suggest that EfDRV is exogenous. As all members of Deltaretrovirus are associated with T- and B-cell malignancies or neurologic disease, further studies on possible zoonosis are warranted.


Assuntos
Quirópteros/virologia , Deltaretrovirus/genética , Deltaretrovirus/isolamento & purificação , Genoma Viral/genética , Animais , Produtos do Gene tax/genética , Humanos , RNA Viral/genética , South Dakota , Estados Unidos , Zoonoses/virologia
4.
Viruses ; 12(7)2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674309

RESUMO

Basic leucine zipper (bZIP) transcription factors (TFs) govern diverse cellular processes and cell fate decisions. The hallmark of the leucine zipper domain is the heptad repeat, with leucine residues at every seventh position in the domain. These leucine residues enable homo- and heterodimerization between ZIP domain α-helices, generating coiled-coil structures that stabilize interactions between adjacent DNA-binding domains and target DNA substrates. Several cancer-causing viruses encode viral bZIP TFs, including human T-cell leukemia virus (HTLV), hepatitis C virus (HCV) and the herpesviruses Marek's disease virus (MDV), Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV). Here, we provide a comprehensive review of these viral bZIP TFs and their impact on viral replication, host cell responses and cell fate.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/fisiologia , Vírus Oncogênicos/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Deltaretrovirus/genética , Deltaretrovirus/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/metabolismo , Humanos , Mardivirus/genética , Mardivirus/metabolismo , Filogenia , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/virologia , Resposta a Proteínas não Dobradas
5.
Blood ; 135(12): 887-889, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191800
6.
Retrovirology ; 16(1): 33, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775783

RESUMO

The Deltaretrovirus genus of retroviruses (family Retroviridae) includes the human T cell leukemia viruses and bovine leukemia virus (BLV). Relatively little is known about the biology and evolution of these viruses, because only a few species have been identified and the genomic 'fossil record' is relatively sparse. Here, we report the discovery of multiple novel endogenous retroviruses (ERVs) derived from ancestral deltaretroviruses. These sequences-two of which contain complete or near complete internal coding regions-reside in genomes of several distinct mammalian orders, including bats, carnivores, cetaceans, and insectivores. We demonstrate that two of these ERVs contain unambiguous homologs of the tax gene, indicating that complex gene regulation has ancient origins within the Deltaretrovirus genus. ERVs demonstrate that the host range of the deltaretrovirus genus is much more extensive than suggested by the relatively small number of exogenous deltaretroviruses described so far, and allow the evolutionary timeline of deltaretrovirus-mammal interaction to be more accurately calibrated.


Assuntos
Deltaretrovirus/genética , Retrovirus Endógenos/genética , Retrovirus Endógenos/isolamento & purificação , Evolução Molecular , Especificidade de Hospedeiro , Mamíferos/virologia , Animais , Genes pX , Genoma Viral , Humanos , Paleontologia , Filogenia
7.
Mol Cancer Res ; 17(12): 2522-2536, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31594868

RESUMO

The genetic and molecular alterations responsible for leukemogenesis and progression of HTLV-infected adult T-cell leukemia (ATL) have not been fully clarified. Previously, we reported that various genes are not only overexpressed but also abnormally spliced in ATL cells. Here, we identified various CASP8 transcript variants in PBMCs from a smoldering-type ATL patient, which encode aberrant truncated caspase 8 (Casp8) isoforms. Among those, we focus on the three transcript variants, CASP8L (including the first 136 bp of the intron 8 between exon 8 and exon 9), CASP8-ΔE4 (without the exon 4), and CASP8-ΔE7 (without the exon 7), because they encode isoforms, Casp8L, Casp8-ΔE4, and Casp8-ΔE7, respectively, without the C-terminal catalytic domains. In this study, we conducted in vitro characterization and functional analysis of those mutant Casp8 isoforms to clarify their changed functions compared with the wild-type (WT)-Casp8. We demonstrated that these abnormal Casp8 isoforms showed lower ability to induce apoptosis than WT-Casp8 due to their dominant-negative interactions with WT-Casp8, which impair WT-Casp8 homodimerization that is essential for induction of apoptosis. Moreover, Casp8L and Casp8-ΔE7, which have only two death-effector domains, significantly activated NFκB by forming filament-like structures, which probably function as scaffolds for the IKK complex formation. In view of increasing levels of these abnormal CASP8 transcripts in primary PBMCs from HTLV-1 carriers and patients with ATL, we propose a possibility that overexpression of those Casp8 mutants, with lower proapoptotic activities and higher NFκB-activating functions than WT-Casp8, may be one of the molecular abnormalities causing malignant transformation and growth of ATL cells. IMPLICATIONS: We describe naturally occurring CASP8 transcription variants in PBMCs from patients with ATL, which encode truncated Casp8-mutant isoforms with lower proapoptotic activities and higher NFκB-activating functions compared with WT-Casp8.


Assuntos
Processamento Alternativo/genética , Caspase 8/genética , Deltaretrovirus/genética , Leucemia de Células T/genética , Apoptose/genética , Caspase 8/sangue , Linhagem Celular Tumoral , Proliferação de Células/genética , Éxons/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia de Células T/sangue , Leucemia de Células T/patologia , Leucemia de Células T/virologia , Masculino , Splicing de RNA/genética , Transdução de Sinais/genética
8.
J Cell Physiol ; 234(11): 21076-21088, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31025383

RESUMO

Intracellular pathogens are subject to elimination by a cellular immune response, and were therefore under evolutionary pressure to develop mechanisms that allow them to inhibit especially this arm of immunity. CD137, a T cell costimulatory molecule, and its ligand, CD137 ligand (CD137L), which is expressed on antigen presenting cells (APC), are potent drivers of cellular cytotoxic immune responses. Here, we report that different viruses usurp a negative feedback mechanism for the CD137-CD137L system that weakens cellular immune responses. Latent membrane protein (LMP)-1 and Tax, oncogenes of Epstein-Barr virus (EBV), and human T-cell lymphotropic virus (HTLV)-1, respectively, induce the expression of CD137. CD137 is transferred by trogocytosis to CD137L-expressing APC, and the CD137-CD137L complex is internalized and degraded, resulting in a reduced CD137-mediated T cell costimulation and a weakened cellular immune response which may facilitate the escape of the virus from immune surveillance. These data identify the usurpation of a CD137-based negative feedback mechanism by intracellular pathogens that enables them to reduce T cell costimulation.


Assuntos
Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Evasão Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Infecções Tumorais por Vírus/imunologia , Ligante 4-1BB/imunologia , Ligante 4-1BB/metabolismo , Animais , Células Apresentadoras de Antígenos/imunologia , Cricetinae , Deltaretrovirus/imunologia , Deltaretrovirus/patogenicidade , Genes Virais , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Camundongos , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Virulência
9.
CuidArte, Enferm ; 13(1): 9-13, jan.2019.
Artigo em Português | BDENF - Enfermagem | ID: biblio-1010389

RESUMO

Introdução: A melhor forma de nutrição de um recém-nascido até os seis meses de vida é p leite materno. Algumas mães não conseguem lactar suficientemente para suprir a amamentação de seu bebê e com isso recorrem ao banco de leite humano. Objetivos: Investigar na literatura científica as regras aplicadas aos bancos de leite mundiais quanto à sorologia do vírus HTLV e compará-las ao Brasil, bem como buscar dados quanto aos efeitos da administração para bebês de leite materno de mulheres portadoras deste vírus....(AU)


Introduction: The best form of nutrition for a newborn up to six months of age is breast milk. Some mothers are unable to breastfeed sufficiently to supply their baby's breastfeeding and so resort to the human milk bank. Objectives: To investigate in the scientific literature the rules applied to the global milk banks regarding the serology of the HTLV virus and compare them to Brazil, as well as to search data about the effects of the administration to breast milk of women with this virus...(AU)


Introducción: la mejor forma de nutrición para un recién nacido hasta los seis meses de edad es la leche materna. Algunas madres no pueden amamantar lo suficiente como para alimentar a sus bebés y recurren al banco de leche humana. Objetivos: Investigar en la literatura científica las reglas aplicadas a los bancos mundiales de leche con respecto a la serología del virus HTLV y compararlas con Brasil, así como buscar datos sobre los efectos de la administración a la leche materna de mujeres con este virus...(AU)


Assuntos
Humanos , Lactente , Serviços de Saúde da Criança , Bancos de Leite , Deltaretrovirus , Nutrição do Lactente , Aleitamento Materno , Saúde Materno-Infantil
10.
J Am Acad Dermatol ; 81(1): 23-41, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30502415

RESUMO

In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.


Assuntos
Deltaretrovirus/patogenicidade , Herpesviridae/patogenicidade , Retroviridae/patogenicidade , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Terapia Combinada , Deltaretrovirus/isolamento & purificação , Educação Médica Continuada , Feminino , Vírus de Hepatite/isolamento & purificação , Vírus de Hepatite/patogenicidade , Herpesviridae/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/patogenicidade , Humanos , Masculino , Prevenção Primária , Prognóstico , Retroviridae/isolamento & purificação , Medição de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/fisiopatologia , Neoplasias Cutâneas/terapia , Análise de Sobrevida , Infecções Tumorais por Vírus/fisiopatologia , Infecções Tumorais por Vírus/terapia
11.
Braz J Infect Dis ; 22(3): 224-234, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29879426

RESUMO

Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing the possible re-emergence of HTLV in West Africa since discovery, a systematic review was carried out, focusing on the distribution of the virus types and significance of frequent indeterminate reports, while highlighting the need for mandatory routine blood screening. Capturing relevant data from discovery till date, sources searched were Google Scholar, CrossRef, NCBI (PubMed), MEDLINE, Research Gate, Mendeley, abstracts of Conferences and Proceedings, organization websites and reference lists of selected papers. A total of 2626 references were initially retrieved using search terms: Worldwide prevalence of HTLV, HTLV in Africa, HTLV in West Africa, HTLV subtypes, HTLV 3 and 4 in Africa, HTLV of African origin, HTLV seroindeterminate results, Spread of HTLV. These references were rigorously trimmed down to 76. Although evidence shows that HTLV is still endemic in the region, West Africa lacks recent epidemiological prevalence data. Thorough investigations are needed to ascertain the true cause of indeterminate Western Blot results. It is imperative that routine screening for HTLVs be mandated in West African health care facilities.


Assuntos
Infecções por Deltaretrovirus/epidemiologia , Deltaretrovirus , África Ocidental/epidemiologia , Infecções por Deltaretrovirus/transmissão , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos
12.
Braz. j. infect. dis ; 22(3): 224-234, May-June 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-974211

RESUMO

ABSTRACT Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing the possible re-emergence of HTLV in West Africa since discovery, a systematic review was carried out, focusing on the distribution of the virus types and significance of frequent indeterminate reports, while highlighting the need for mandatory routine blood screening. Capturing relevant data from discovery till date, sources searched were Google Scholar, CrossRef, NCBI (PubMed), MEDLINE, Research Gate, Mendeley, abstracts of Conferences and Proceedings, organization websites and reference lists of selected papers. A total of 2626 references were initially retrieved using search terms: Worldwide prevalence of HTLV, HTLV in Africa, HTLV in West Africa, HTLV subtypes, HTLV 3 and 4 in Africa, HTLV of African origin, HTLV seroindeterminate results, Spread of HTLV. These references were rigorously trimmed down to 76. Although evidence shows that HTLV is still endemic in the region, West Africa lacks recent epidemiological prevalence data. Thorough investigations are needed to ascertain the true cause of indeterminate Western Blot results. It is imperative that routine screening for HTLVs be mandated in West African health care facilities.


Assuntos
Humanos , Masculino , Feminino , Infecções por Deltaretrovirus/epidemiologia , Deltaretrovirus , Infecções por Deltaretrovirus/transmissão , Estudos Soroepidemiológicos , Prevalência , Fatores de Risco , África Ocidental/epidemiologia
13.
BMC Pregnancy Childbirth ; 18(1): 169, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769062

RESUMO

BACKGROUND: Prenatal tests are important for prevention of vertical transmission of various infectious agents. The objective of this study was to describe the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), cytomegalovirus (CMV), rubella virus and vaccination coverage against HBV in pregnant adolescents who received care in the city of Belém, Pará, Brazil. METHODS: A cross-sectional study was performed with 324 pregnant adolescents from 2009 to 2010. After the interview and blood collection, the patients were screened for antibodies and/or antigens against HIV-1/2, HTLV-1/2, CMV, rubella virus and HBV. The epidemiological variables were demonstrated using descriptive statistics with the G, χ2 and Fisher exact tests. RESULTS: The mean age of the participants was 15.8 years, and the majority (65.4%) had less than 6 years of education. The mean age at first intercourse was 14.4 years, and 60.8% reported having a partner aged between 12 and 14 years. The prevalence of HIV infection was 0.3%, and of HTLV infection was 0.6%. Regarding HBV, 0.6% of the participants had acute infection, 9.9% had a previous infection, 16.7% had vaccine immunity and 72.8% were susceptible to infection. The presence of anti-HBs was greater in adolescent between 12 and 14 years old (28.8%) while the anti-HBc was greater in adolescent between 15 and 18 years old (10.3%). Most of the adolescents presented the IgG antibody to CMV (96.3%) and rubella (92.3%). None of the participants had acute rubella infection, and 2.2% had anti-CMV IgM. CONCLUSIONS: This study is the first report of the seroepidemiology of infectious agents in a population of pregnant adolescents in the Northern region of Brazil. Most of the adolescents had low levels of education, were susceptible to HBV infection and had IgG antibodies to CMV and rubella virus. The prevalence of HBV, HIV and HTLV was similar to that reported in other regions of Brazil. However, the presence of these agents in this younger population reinforces the need for good prenatal follow-up and more comprehensive vaccination campaigns against HBV due to the large number of women susceptible to the virus.


Assuntos
Anticorpos Antivirais/sangue , Testes para Triagem do Soro Materno/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Gravidez na Adolescência/sangue , Viroses/epidemiologia , Adolescente , Anticorpos Antivirais/imunologia , Brasil/epidemiologia , Criança , Estudos Transversais , Citomegalovirus/imunologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Deltaretrovirus/imunologia , Infecções por Deltaretrovirus/sangue , Infecções por Deltaretrovirus/epidemiologia , Infecções por Deltaretrovirus/virologia , Feminino , HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologia , Cuidado Pré-Natal , Rubéola (Sarampo Alemão)/sangue , Rubéola (Sarampo Alemão)/epidemiologia , Rubéola (Sarampo Alemão)/virologia , Vírus da Rubéola/imunologia , Estudos Soroepidemiológicos , Viroses/sangue , Viroses/virologia
14.
Viruses ; 10(4)2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29642581

RESUMO

Endogenous retrovirus (ERV) sequences provide a rich source of information about the long-term interactions between retroviruses and their hosts. However, most ERVs are derived from a subset of retrovirus groups, while ERVs derived from certain other groups remain extremely rare. In particular, only a single ERV sequence has been identified that shows evidence of being related to an ancient Deltaretrovirus, despite the large number of vertebrate genome sequences now available. In this report, we identify a second example of an ERV sequence putatively derived from a past deltaretroviral infection, in the genomes of several species of horseshoe bats (Rhinolophidae). This sequence represents a fragment of viral genome derived from a single integration. The time of the integration was estimated to be 11-19 million years ago. This finding, together with the previously identified endogenous Deltaretrovirus in long-fingered bats (Miniopteridae), suggest a close association of bats with ancient deltaretroviruses.


Assuntos
Quirópteros/virologia , Deltaretrovirus/genética , Retrovirus Endógenos/genética , Genoma/genética , Animais , Quirópteros/classificação , Deltaretrovirus/classificação , Retrovirus Endógenos/classificação , Evolução Molecular , Genômica , Filogenia , Recombinação Genética , Sequências Repetidas Terminais/genética
15.
Braz. j. infect. dis ; 22(2): 106-112, Mar.-Apr. 2018. tab, graf
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-951631

RESUMO

ABSTRACT Background: Infection with Human T cell Leukemia Virus type 1 can be associated with myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. Lymphocytes from about half of Human T cell Leukemia Virus type 1-infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease and viral burden is poorly understood. Objective: To evaluate T-cell proliferation in vitro among patients co-infected with Human T cell Leukemia Virus type 1/Hepatitis C Virus/Human Immunodeficiency Virus type 1. Material and methods: From 610 Human T cell Leukemia Virus-infected patients of the Human T cell Leukemia Virus outpatient clinic from Institute of Infectious Diseases "Emilio Ribas" in São Paulo, 273 agreed to participate: 72 had HAM/TSP (excluded from this analysis) and 201 were asymptomatic, a classification performed during a regular neurological appointment. We selected the subgroup made up only by the 201 asymptomatic subjects to avoid bias by the clinical status as a confounder effect, who had laboratory results of Human T cell Leukemia Virus type 1 proviral load and T-cell proliferation assay in our database. They were further grouped according to their serological status in four categories: 121 Human T cell Leukemia Virus type 1 asymptomatic mono-infected carriers; 32 Human T cell Leukemia Virus type 1/Hepatitis C Virus, 29 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1, and 19 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1/Hepatitis C Virus co-infected patients. Clinical data were obtained from medical records and interviews. DNA Human T cell Leukemia Virus type 1 proviral load (PVL) and T-cell proliferation (LPA) assay were performed for all samples. Results: From a total of 273 subjects with Human T cell Leukemia Virus type 1, 80 presented co-infections: 29 had Human Immunodeficiency Virus type 1, 32 had Hepatitis C Virus, and 19 had Human Immunodeficiency Virus type 1 and Hepatitis C Virus. Comparing the groups based on their serological status, independently of being asymptomatic carriers, we observed a significant increase of PVL (p < 0.001) and LPA (p = 0.001). However, when groups were stratified according to their clinical and serological status, there was no significant increase in Human T cell Leukemia Virus type 1 PVL and LPA. Conclusion: No significant increase of basal T-cell proliferation among Human T cell Leukemia Virus type 1 co-infected was observed. This interaction may be implicated in liver damage, worsening the prognosis of co-infected patients or, on the contrary, inducing a higher spontaneous clearance of Hepatitis C Virus infection in Human T cell Leukemia Virus type 1 co-infected patients.


Assuntos
Humanos , Adolescente , Infecções por HIV , Hepatite C , Deltaretrovirus/crescimento & desenvolvimento
16.
Boletim epidemiológico paulista ; 15(179-180): 11-14, 2018.
Artigo em Português | Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-ACVSES | ID: biblio-1061559
17.
J Virol ; 91(16)2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28615198

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 cell-to-cell transmission is dependent on the release of infectious virus particles into the virological synapse. The HTLV-1 particle structure is still poorly understood, and previous studies analyzed viruses produced by transformed lymphocytic cell lines chronically infected with HTLV-1, particularly the MT-2 cell line, which harbors truncated proviruses and expresses aberrant forms of the Gag protein. In this study, we demonstrate that the chronically infected SP cell line harbors a relatively low number of proviruses, making it a more promising experimental system for the study of the HTLV-1 particle structure. We first identified the genomic sites of integration and characterized the genetic structure of the gag region in each provirus. We also determined that despite encoding a truncated Gag protein, only the full-length Gag protein was incorporated into virus particles. Cryo-transmission electron microscopy analyses of the purified virus particles revealed three classes of particles based upon capsid core morphology: complete cores, incomplete cores, and particles without distinct electron densities that would correlate with the capsid region of a core structure. Observed cores were generally polygonal, and virus particles were on average 115 nm in diameter. These data corroborate particle morphologies previously observed for MT-2 cells and provide evidence that the known poor infectivity of HTLV-1 particles may correlate with HTLV-1 particle populations containing few virus particles possessing a complete capsid core structure.IMPORTANCE Studies of retroviral particle core morphology have demonstrated a correlation between capsid core stability and the relative infectivity of the virus. In this study, we used cryo-transmission electron microscopy to demonstrate that HTLV-1 particles produced from a distinct chronically infected cell line are polymorphic in nature, with many particles lacking organized electron densities that would correlate with a complete core structure. These findings have important implications for infectious HTLV-1 spread, particularly in the context of cell-to-cell transmission, a critical step in HTLV-1 transmission and pathogenesis.


Assuntos
Deltaretrovirus/fisiologia , Deltaretrovirus/ultraestrutura , Provírus/genética , Vírion/ultraestrutura , Integração Viral , Linhagem Celular , Microscopia Crioeletrônica , Deltaretrovirus/genética , Humanos
18.
Proc Natl Acad Sci U S A ; 114(12): 3145-3150, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28280099

RESUMO

Retroviruses can create endogenous forms on infiltration into the germline cells of their hosts. These forms are then vertically transmitted and can be considered as genetic fossils of ancient viruses. All retrovirus genera, with the exception of deltaretroviruses, have had their representation identified in the host genome as a virus fossil record. Here we describe an endogenous Deltaretrovirus, identified in the germline of long-fingered bats (Miniopteridae). A single, heavily deleted copy of this retrovirus has been found in the genome of miniopterid species, but not in the genomes of the phylogenetically closest bat families, Vespertilionidae and Cistugonidae. Therefore, the endogenization occurred in a time interval between 20 and 45 million years ago. This discovery closes the last major gap in the retroviral fossil record and provides important insights into the history of deltaretroviruses in mammals.


Assuntos
Quirópteros/genética , Deltaretrovirus/genética , Retrovirus Endógenos/genética , Genoma , Animais , Sequência de Bases , Quirópteros/classificação , Sequência Consenso , Evolução Molecular , Genes Virais , Genômica/métodos , Conformação de Ácido Nucleico , Fases de Leitura Aberta , Filogenia
19.
Clin Infect Dis ; 63(6): 800-803, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27325689

RESUMO

Molecular screening of 300 at-risk people from Central Africa identified 2 human T-lymphotropic virus (HTLV)-4-infected individuals. A zoonotic origin of infection was suggested, as both individuals reported being severely bitten by a gorilla during hunting activities. One strain was highly divergent and was designated as the HTLV-4 subtype-b prototype.


Assuntos
Mordeduras e Picadas/virologia , Infecções por Deltaretrovirus , Deltaretrovirus/genética , Gorilla gorilla/virologia , Zoonoses , Idoso , Animais , DNA Viral/sangue , DNA Viral/genética , Infecções por Deltaretrovirus/transmissão , Infecções por Deltaretrovirus/veterinária , Infecções por Deltaretrovirus/virologia , Gabão , Humanos , Masculino , Pessoa de Meia-Idade , Zoonoses/transmissão , Zoonoses/virologia
20.
Nucleic Acids Res ; 44(1): 364-76, 2016 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-26657642

RESUMO

To establish infection, a retrovirus must insert a DNA copy of its RNA genome into host chromatin. This reaction is catalysed by the virally encoded enzyme integrase (IN) and is facilitated by viral genus-specific host factors. Herein, cellular serine/threonine protein phosphatase 2A (PP2A) is identified as a functional IN binding partner exclusive to δ-retroviruses, including human T cell lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2) and bovine leukaemia virus (BLV). PP2A is a heterotrimer composed of a scaffold, catalytic and one of any of four families of regulatory subunits, and the interaction is specific to the B' family of the regulatory subunits. B'-PP2A and HTLV-1 IN display nuclear co-localization, and the B' subunit stimulates concerted strand transfer activity of δ-retroviral INs in vitro. The protein-protein interaction interface maps to a patch of highly conserved residues on B', which when mutated render B' incapable of binding to and stimulating HTLV-1 and -2 IN strand transfer activity.


Assuntos
Deltaretrovirus/metabolismo , Integrases/metabolismo , Proteína Fosfatase 2/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Transporte/metabolismo , Bovinos , Linhagem Celular , Deltaretrovirus/enzimologia , Ativação Enzimática , Vírus Linfotrópico T Tipo 1 Humano/enzimologia , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Vírus da Leucemia Bovina/enzimologia , Vírus da Leucemia Bovina/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Proteína Fosfatase 2/química , Subunidades Proteicas , Alinhamento de Sequência , Integração Viral
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