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1.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46946

RESUMO

Portal do Ministério da Saúde- Publicado: Segunda, 20 de Janeiro de 2020, 21h28 Apresenta um vídeo com esclarecimentos sobre o Arenavírus, informa sobre a situação atual do virús em São Paulo e disponibiliza o Boletim epidemiológico


Assuntos
Arenavirus/patogenicidade , Febre Hemorrágica Americana/virologia , Evolução Fatal
2.
Viruses ; 11(3)2019 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-30909570

RESUMO

Lassa virus (LASV) and Mopeia virus (MOPV) are two closely related Old-World mammarenaviruses. LASV causes severe hemorrhagic fever with high mortality in humans, whereas no case of MOPV infection has been reported. Comparing MOPV and LASV is a powerful strategy to unravel pathogenic mechanisms that occur during the course of pathogenic arenavirus infection. We used a yeast two-hybrid approach to identify cell partners of MOPV and LASV Z matrix protein in which two autophagy adaptors were identified, NDP52 and TAX1BP1. Autophagy has emerged as an important cellular defense mechanism against viral infections but its role during arenavirus infection has not been shown. Here, we demonstrate that autophagy is transiently induced by MOPV, but not LASV, in infected cells two days after infection. Impairment of the early steps of autophagy significantly decreased the production of MOPV and LASV infectious particles, whereas a blockade of the degradative steps impaired only MOPV infectious particle production. Our study provides insights into the role played by autophagy during MOPV and LASV infection and suggests that this process could partially explain their different pathogenicity.


Assuntos
Arenavirus/fisiologia , Autofagia , Vírus Lassa/fisiologia , Animais , Arenavirus/patogenicidade , Células HEK293 , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Vírus Lassa/patogenicidade , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Técnicas do Sistema de Duplo-Híbrido , Células Vero
3.
J Virol ; 92(13)2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29669840

RESUMO

RIG-I is a major cytoplasmic sensor of viral pathogen-associated molecular pattern (PAMP) RNA and induces type I interferon (IFN) production upon viral infection. A double-stranded RNA (dsRNA)-binding protein, PACT, plays an important role in potentiating RIG-I function. We have shown previously that arenaviral nucleoproteins (NPs) suppress type I IFN production via their RNase activity to degrade PAMP RNA. We report here that NPs of arenaviruses block the PACT-induced enhancement of RIG-I function to mediate type I IFN production and that this inhibition is dependent on the RNase function of NPs, which is different from that of a known mechanism of other viral proteins to abolish the interaction between PACT and RIG-I. To understand the biological roles of PACT and RIG-I in authentic arenavirus infection, we analyze growth kinetics of recombinant Pichinde virus (PICV), a prototypical arenavirus, in RIG-I knockout (KO) and PACT KO mouse embryonic fibroblast (MEF) cells. Wild-type (WT) PICV grew at higher titers in both KO MEF lines than in normal MEFs, suggesting the important roles of these cellular proteins in restricting virus replication. PICV carrying the NP RNase catalytically inactive mutation could not grow in normal MEFs but could replicate to some extent in both KO MEF lines. The level of virus growth was inversely correlated with the amount of type I IFNs produced. These results suggest that PACT plays an important role in potentiating RIG-I function to produce type I IFNs in order to restrict arenavirus replication and that viral NP RNase activity is essential for optimal viral replication by suppressing PACT-induced RIG-I activation.IMPORTANCE We report here a new role of the nucleoproteins of arenaviruses that can block type I IFN production via their specific inhibition of the cellular protein sensors of virus infection (RIG-I and PACT). Our results suggest that PACT plays an important role in potentiating RIG-I function to produce type I IFNs in order to restrict arenavirus replication. This new knowledge can be exploited for the development of novel antiviral treatments and/or vaccines against some arenaviruses that can cause severe and lethal hemorrhagic fever diseases in humans.


Assuntos
Arenavirus/patogenicidade , Interações Hospedeiro-Patógeno , Interferon Tipo I/metabolismo , Nucleoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores do Ácido Retinoico/metabolismo , Proteínas Virais/metabolismo , Infecções por Arenaviridae/genética , Infecções por Arenaviridae/metabolismo , Infecções por Arenaviridae/virologia , Células HEK293 , Humanos , Nucleoproteínas/genética , Vírus Pichinde/fisiologia , Proteínas de Ligação a RNA/genética , Receptores do Ácido Retinoico/genética , Proteínas Virais/genética , Replicação Viral
4.
Methods Mol Biol ; 1604: 55-78, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28986825

RESUMO

This article will outline surveillance approaches for viral hemorrhagic fevers. Specific methods for surveillance of clinical samples will be emphasized. Separate articles will describe methods for surveillance of rodent-borne viruses (roboviruses) and arthropod-borne viruses (arboviruses). Since the appearance of hantaviruses and arenaviruses in the Americas, more than 30 different species in each group have been established, and therefore they have become the most frequently emerging viruses. Flaviviruses such as yellow fever and dengue viruses, although easier to recognize, are also more widely spread and therefore considered a very important public health issue, particularly for under-developed countries. On the other hand, marburgviruses and ebolaviruses, previously thought to be restricted to the African continent, have recently been shown to be more global. For many of these agents virus isolation has been a challenging task: trapping the specific vectors (mosquitoes and ticks), and reservoirs (rodents and bats), or obtaining the samples from suspected clinical human cases demands special protective gear, uncommon devices (respirators), special facilities (BSL-3 and 4), and particular skills to recognize the slow and inapparent cytopathic effects in cell culture. Alternatively, serological and molecular approaches have been very helpful in discovering and describing newly emerging viruses in many areas where the previous resources are unavailable. Unfortunately, in many cases, detailed studies have been performed only after outbreaks occur, and then active surveillance is needed to prevent viral dissemination in human populations.


Assuntos
Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/genética , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/genética , Animais , Arbovirus/genética , Arbovirus/patogenicidade , Arenavirus/genética , Arenavirus/patogenicidade , Hantavirus/genética , Hantavirus/patogenicidade , Febre Hemorrágica com Síndrome Renal/virologia , Febres Hemorrágicas Virais/virologia , Humanos , Saúde Pública
5.
Methods Mol Biol ; 1604: 257-267, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28986841

RESUMO

Hemorrhagic fever (HF) viruses, such as Lassa, Ebola, and dengue viruses, represent major human health risks due to their highly contagious nature, the severity of the clinical manifestations induced, the lack of vaccines, and the very limited therapeutic options currently available. Appropriate animal models are obviously critical to study disease pathogenesis and develop efficient therapies. We recently reported that the clone 13 (Cl13) variant of the lymphocytic choriomeningitis virus (LCMV-Cl13), a prototype arenavirus closely related to Lassa virus, causes in some mouse strains endothelial damage, vascular leakage, platelet loss, and death, mimicking pathological aspects typically observed in Lassa and other HF syndromes. This model has the advantage that the mice used are fully immunocompetent, allowing studies on the contribution of the immune response to disease progression. Moreover, LCMV is very well characterized and exhibits limited pathogenicity in humans, allowing handling in convenient BSL-2 facilities. In this chapter we outline protocols for the induction and analysis of arenavirus-mediated pathogenesis in the NZB/LCMV model, including mouse infection, virus titer determination, platelet counting, phenotypic analysis of virus-specific T cells, and assessment of vascular permeability.


Assuntos
Febres Hemorrágicas Virais/virologia , Vírus da Coriomeningite Linfocítica/patogenicidade , Animais , Arenavirus/genética , Arenavirus/patogenicidade , Lavagem Broncoalveolar , Modelos Animais de Doenças , Vírus Lassa/genética , Vírus Lassa/patogenicidade , Vírus da Coriomeningite Linfocítica/genética , Camundongos , Contagem de Plaquetas , Vacinas Virais
6.
Methods Mol Biol ; 1604: 291-302, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28986844

RESUMO

Viral hemorrhagic fevers affect liver functions such as important metabolic processes and the replacement of new blood cells, coagulation factors, and growth factors. Typically, multi-organ diseases such as viral hemorrhagic fevers are studied in an organism, but it is also possible to derive information about the molecular events involved in disease processes by focusing on liver cell culture. Here we describe a multi-cell culture system that is capable of replicating the arenavirus LCMV-WE, a virus that can cause hemorrhagic fever in primates, as a model for liver infection by a hemorrhagic fever virus.


Assuntos
Febres Hemorrágicas Virais/virologia , Hepatopatias/virologia , Fígado/virologia , Arenavirus/genética , Arenavirus/patogenicidade , Febres Hemorrágicas Virais/genética , Humanos , Cultura Primária de Células
7.
Uirusu ; 68(1): 51-62, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-31105135

RESUMO

Arenavirus is a genetic term for viruses belonging to the family Arenaviridae and is presented from lymphocytic choriomeningitis virus (LCMV), which shows almost no pathogenicity to humans, to Lassa virus, Junin virus, Machupo virus, Chapare virus, Lujo virus, Sabia virus, and Guanarito virus, which shows high pathogenicity to humans. These viruses except for LCMV are risk group 4 pathogens specified by World Health Organization. Based on this designation, it is designated as Class I pathogens in Japan. Although there have been no reports excluding one imported case of the Lassa fever patient, it is not surprising whenever imported cases occur in our country. Considering the disease severity and mortality rate, it is an urgent matter to develop vaccines and therapeutic drugs in endemic areas, and maintenances of these are also important in countries other than endemic areas. However, basic research on highly pathogenic arenavirus infections and development of therapeutic drugs are not easily progressed, because handling in highly safe research facilities is indispensable. In this article, we will outline the current knowledge from the recent basic research on arenavirus to the development situation of antivirals against arenaviruses.


Assuntos
Antivirais , Infecções por Arenaviridae/tratamento farmacológico , Infecções por Arenaviridae/virologia , Arenavirus/classificação , Arenavirus/patogenicidade , Descoberta de Drogas , África Ocidental/epidemiologia , Infecções por Arenaviridae/epidemiologia , Infecções por Arenaviridae/prevenção & controle , Arenavirus/genética , Arenavirus/fisiologia , Surtos de Doenças , Descoberta de Drogas/tendências , Genoma Viral/genética , Humanos , Pesquisa/tendências , Transcrição Genética , Vacinas Virais , Vírion
8.
Ecohealth ; 14(3): 463-473, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28616660

RESUMO

Infectious diseases of wildlife are typically studied using data on antibody and pathogen levels. In order to interpret these data, it is necessary to know the course of antibodies and pathogen levels after infection. Such data are typically collected using experimental infection studies in which host individuals are inoculated in the laboratory and sampled over an extended period, but because laboratory conditions are controlled and much less variable than natural conditions, the immune response and pathogen dynamics may differ. Here, we compared Morogoro arenavirus infection patterns between naturally and experimentally infected multimammate mice (Mastomys natalensis). Longitudinal samples were collected during three months of bi-weekly trapping in Morogoro, Tanzania, and antibody titer and viral RNA presence were determined. The time of infection was estimated from these data using a recently developed Bayesian approach, which allowed us to assess whether the natural temporal patterns match the previously observed patterns in the laboratory. A good match was found for 52% of naturally infected individuals, while most of the mismatches can be explained by the presence of chronically infected individuals (35%), maternal antibodies (10%), and an antibody detection limit (25%). These results suggest that while laboratory data are useful for interpreting field samples, there can still be differences due to conditions that were not tested in the laboratory.


Assuntos
Animais Selvagens/virologia , Infecções por Arenaviridae/imunologia , Infecções por Arenaviridae/patologia , Arenavirus/patogenicidade , Reservatórios de Doenças/virologia , Camundongos/virologia , Doenças dos Roedores/virologia , Animais , Animais Selvagens/imunologia , Arenavirus/imunologia , Doenças dos Roedores/imunologia , Doenças dos Roedores/patologia , Tanzânia
9.
J Virol ; 90(8): 3810-3818, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26865707

RESUMO

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.


Assuntos
Infecções por Arenaviridae/imunologia , Arenavirus/imunologia , Arenavirus/patogenicidade , Imunidade Inata , Animais , Febres Hemorrágicas Virais/imunologia , Febres Hemorrágicas Virais/virologia , Humanos , Evasão da Resposta Imune , Interferons/antagonistas & inibidores , Dedos de Zinco
10.
Biomed Res Int ; 2015: 793257, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26266264

RESUMO

Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs.


Assuntos
Arenavirus/patogenicidade , Infecções por Hantavirus/virologia , Hantavirus/patogenicidade , Febres Hemorrágicas Virais/virologia , Animais , Reservatórios de Doenças , Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/patologia , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/patologia , Humanos , Modelos Animais , Roedores/virologia
11.
Sci Rep ; 5: 10445, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26022445

RESUMO

Arenaviruses can cause mild to severe hemorrhagic fevers. Humans mainly get infected through contact with infected rodents or their excretions, yet little is known about transmission dynamics within rodent populations. Morogoro virus (MORV) is an Old World arenavirus closely related to Lassa virus with which it shares the same host species Mastomys natalensis. We injected MORV in its host, and sampled blood and excretions at frequent intervals. Infection in adults was acute; viral RNA disappeared from blood after 18 days post infection (dpi) and from excretions after 39 dpi. Antibodies were present from 7 dpi and never disappeared. Neonatally infected animals acquired a chronic infection with RNA and antibodies in blood for at least 3 months. The quantified excretion and antibody patterns can be used to inform mathematical transmission models, and are essential for understanding and controlling transmission in the natural rodent host populations.


Assuntos
Infecções por Arenaviridae/transmissão , Arenavirus/patogenicidade , Vírus Lassa/patogenicidade , Animais , Anticorpos Antivirais/sangue , Infecções por Arenaviridae/patologia , Infecções por Arenaviridae/virologia , Arenavirus/genética , Reservatórios de Doenças/virologia , Humanos , Vírus Lassa/genética , Murinae/virologia , RNA Viral/sangue , Tanzânia
12.
J Clin Virol ; 64: 120-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25549822

RESUMO

Significant progress has been made in the past 10 years in unraveling the molecular biology of highly pathogenic arenaviruses that are endemic in several West African countries (Lassa fever virus) and in some regions of South America (Argentine and Bolivian hemorrhagic fever viruses). While this has resulted in proof-of-concept studies of novel vaccine candidates in non-human primates and in the discovery of several novel antiviral small molecule drug candidates, none of them has been tested in the clinic to date. The recent Ebola outbreak in West Africa has demonstrated very clearly that there is an urgent need to develop the prophylactic and therapeutic armamentarium against viral hemorrhagic fever viruses as part of a global preparedness for future epidemics. As it pertains to this goal, the present article summarizes the current knowledge of highly pathogenic arenaviruses and identifies opportunities for translational research.


Assuntos
Antivirais/uso terapêutico , Infecções por Arenaviridae/epidemiologia , Infecções por Arenaviridae/terapia , Pesquisa Biomédica , Febre Lassa/epidemiologia , Febre Lassa/terapia , Vacinas Virais , África Ocidental/epidemiologia , Animais , Arenavirus/patogenicidade , Argentina/epidemiologia , Bolívia/epidemiologia , Epidemias/prevenção & controle , Febres Hemorrágicas Virais/diagnóstico , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/terapia , Humanos , Febre Lassa/diagnóstico , Vírus Lassa/patogenicidade
13.
PLoS One ; 8(8): e72290, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23991083

RESUMO

Lassa virus causes hemorrhagic Lassa fever in humans, while the related Old World arenaviruses Mopeia, Morogoro, and Mobala are supposedly apathogenic to humans and cause only inapparent infection in non-human primates. Here, we studied whether the virulence of Old World arenaviruses in humans and non-human primates is reflected in type I interferon receptor deficient (IFNAR(-/-)) mice by testing several strains of Lassa virus vs. the apathogenic viruses Mopeia, Morogoro, and Mobala. All Lassa virus strains tested-Josiah, AV, BA366, and Nig04-10-replicated to high titers in blood, lung, kidney, heart, spleen, brain, and liver and caused disease as evidenced by weight loss and elevation of aspartate and alanine aminotransferase (AST and ALT) levels with a high AST/ALT ratio. Lassa fever-like pathology included acute hepatitis, interstitial pneumonia, and pronounced disturbance of splenic cytoarchitecture. Infiltrations of activated monocytes/macrophages expressing inducible nitric oxide synthase and T cells were found in liver and lung. In contrast, Mopeia, Morogoro, and Mobala virus replicated poorly in the animals and acute inflammatory alterations were not noted. Depletion of CD4(+) and CD8(+) T cells strongly enhanced susceptibility of IFNAR(-/-) mice to the apathogenic viruses. In conclusion, the virulence of Old World arenaviruses in IFNAR(-/-) mice correlates with their virulence in humans and non-human primates. In addition to the type I interferon system, T cells seem to regulate whether or not an arenavirus can productively infect non-host rodent species. The observation that Lassa virus overcomes the species barrier without artificial depletion of T cells suggests it is able to impair T cell functionality in a way that corresponds to depletion.


Assuntos
Infecções por Arenaviridae/virologia , Arenavirus/patogenicidade , Receptor de Interferon alfa e beta/fisiologia , Animais , Infecções por Arenaviridae/imunologia , Infecções por Arenaviridae/patologia , Interações Hospedeiro-Patógeno , Depleção Linfocítica , Camundongos , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Linfócitos T/imunologia , Virulência
14.
Viruses ; 5(1): 340-51, 2013 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-23337384

RESUMO

Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.


Assuntos
Infecções por Arenaviridae/virologia , Arenavirus/patogenicidade , Febres Hemorrágicas Virais/virologia , Animais , Arenavirus/genética , Arenavirus/fisiologia , Fatores de Coagulação Sanguínea/metabolismo , Febres Hemorrágicas Virais/sangue , Febres Hemorrágicas Virais/metabolismo , Febres Hemorrágicas Virais/fisiopatologia , Humanos , Contagem de Plaquetas
15.
Antiviral Res ; 97(2): 81-92, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23261843

RESUMO

A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Africa, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNß) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies.


Assuntos
Arenavirus/patogenicidade , Febre Hemorrágica Americana/patologia , Febre Hemorrágica Americana/virologia , Interações Hospedeiro-Patógeno , Proteínas Virais/metabolismo , Fatores de Virulência/metabolismo , Febre Hemorrágica Americana/prevenção & controle , Febre Hemorrágica Americana/terapia , Humanos , Proteínas Virais/antagonistas & inibidores , Fatores de Virulência/antagonistas & inibidores
16.
Viruses ; 4(10): 2049-79, 2012 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-23202453

RESUMO

Arenaviruses have a bisegmented negative-strand RNA genome, which encodes four viral proteins: GP and NP by the S segment and L and Z by the L segment. These four viral proteins possess multiple functions in infection, replication and release of progeny viruses from infected cells. The small RING finger protein, Z protein is a matrix protein that plays a central role in viral assembly and budding. Although all arenaviruses encode Z protein, amino acid sequence alignment showed a huge variety among the species, especially at the C-terminus where the L-domain is located. Recent publications have demonstrated the interactions between viral protein and viral protein, and viral protein and host cellular protein, which facilitate transportation and assembly of viral components to sites of virus egress. This review presents a summary of current knowledge regarding arenavirus assembly and budding, in comparison with other enveloped viruses. We also refer to the restriction of arenavirus production by the antiviral cellular factor, Tetherin/BST-2.


Assuntos
Arenavirus/fisiologia , Genoma Viral , Montagem de Vírus , Liberação de Vírus , Sequência de Aminoácidos , Animais , Infecções por Arenaviridae/patologia , Infecções por Arenaviridae/virologia , Arenavirus/genética , Arenavirus/metabolismo , Arenavirus/patogenicidade , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Membrana Celular/virologia , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Transporte Proteico , Relação Estrutura-Atividade
17.
Viruses ; 4(10): 2182-96, 2012 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-23202459

RESUMO

The innate response to infection by an Old World arenavirus is initiated and mediated by extracellular and intracellular receptors, and effector molecules. In response, the invading virus has evolved to inhibit these responses and create the best environment possible for replication and spread. Here, we will discuss both the host's response to infection with data from human infection and lessons learned from animal models, as well as the multitude of ways the virus combats the resulting immune response. Finally, we will highlight recent work identifying TLR2 as an innate sensor for arenaviruses and how the TLR2-dependent response differs depending on the pathogenicity of the strain.


Assuntos
Infecções por Arenaviridae/imunologia , Arenavirus/imunologia , Evasão da Resposta Imune , Imunidade Inata , Imunidade Adaptativa , Animais , Formação de Anticorpos , Infecções por Arenaviridae/virologia , Arenavirus/patogenicidade , Arenavirus/fisiologia , Citocinas/imunologia , Humanos , Memória Imunológica , Inflamação/imunologia , Inflamação/virologia , Interferon Tipo I/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Linfócitos T/imunologia , Linfócitos T/virologia , Receptor 2 Toll-Like/imunologia , Replicação Viral
18.
Viruses ; 4(10): 2162-81, 2012 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-23202458

RESUMO

Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC) by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP). GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.


Assuntos
Arenavirus/metabolismo , Pró-Proteína Convertases/metabolismo , Serina Endopeptidases/metabolismo , Proteínas do Envelope Viral/biossíntese , Sequência de Aminoácidos , Antivirais/farmacologia , Infecções por Arenaviridae/tratamento farmacológico , Infecções por Arenaviridae/metabolismo , Infecções por Arenaviridae/virologia , Arenavirus/efeitos dos fármacos , Arenavirus/patogenicidade , Glicosilação , Complexo de Golgi/metabolismo , Complexo de Golgi/virologia , Humanos , Pró-Proteína Convertases/antagonistas & inibidores , Sinais Direcionadores de Proteínas , Proteólise , Pirrolidinas/farmacologia , Receptores de Superfície Celular/metabolismo , Proteínas do Envelope Viral/química , Montagem de Vírus , Ligação Viral
19.
Viruses ; 4(9): 1569-91, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23170173

RESUMO

Among the members of the Arenaviridae family, Lassa virus and Junin virus generate periodic annual outbreaks of severe human hemorrhagic fever (HF) in endemic areas of West Africa and Argentina, respectively. Given the human health threat that arenaviruses represent and the lack of a specific and safe chemotherapy, the search for effective antiviral compounds is a continuous demanding effort. Since diverse host cell pathways and enzymes are used by RNA viruses to fulfill their replicative cycle, the targeting of a host process has turned an attractive antiviral approach in the last years for many unrelated virus types. This strategy has the additional benefit to reduce the serious challenge for therapy of RNA viruses to escape from drug effects through selection of resistant variants triggered by their high mutation rate. This article focuses on novel strategies to identify inhibitors for arenavirus therapy, analyzing the potential for antiviral developments of diverse host factors essential for virus infection.


Assuntos
Antivirais/metabolismo , Arenavirus/patogenicidade , Interações Hospedeiro-Patógeno , Infecções por Arenaviridae/terapia , Humanos
20.
Viruses ; 4(9): 1802-29, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23170184

RESUMO

Arenaviruses are enveloped, bipartite negative single-stranded RNA viruses that can cause a wide spectrum of disease in humans and experimental animals including hemorrhagic fever. The majority of these viruses are rodent-borne and the arenavirus family can be divided into two groups: the Lassa-Lymphocytic choriomeningitis serocomplex and the Tacaribe serocomplex. Arenavirus-induced disease may include characteristic symptoms ranging from fever, malaise, body aches, petechiae, dehydration, hemorrhage, organ failure, shock, and in severe cases death. Currently, there are few prophylactic and therapeutic treatments available for arenavirus-induced symptoms. Supportive care and ribavirin remain the predominant strategies for treating most of the arenavirus-induced diseases. Therefore, efficacy testing of novel therapeutic and prophylactic strategies in relevant animal models is necessary. Because of the potential for person-to-person spread, the ability to cause lethal or debilitating disease in humans, limited treatment options, and potential as a bio-weapon, the development of prophylactics and therapeutics is essential. This article reviews the current arenavirus animal models and prophylactic and therapeutic strategies under development to treat arenavirus infection.


Assuntos
Antivirais/administração & dosagem , Infecções por Arenaviridae/tratamento farmacológico , Infecções por Arenaviridae/patologia , Arenavirus/patogenicidade , Modelos Animais de Doenças , Animais , Quimioprevenção/métodos , Resultado do Tratamento
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