Presencia de Oligoryzomys microtis (Rodentia) en hábitats silvestres en Bolivia / Presence of Oligoryzomys microtis (Rodentia) in wild habitats in Bolivia

Rodents are very important organisms within ecosystems; however, some species are considered pests because they consume and damage crops and because they are vectors, hosts, or reservoirs in the transmission of emerging infectious diseases. Rodents in Bolivia are represented by 148 species, Oligoryzomys microtis (Allen, 1916) being a species of public health importance because it is considered a potential natural reservoir of the Chapare virus, which causes Chapare Hemorrhagic Fever, and it is a deadly disease for humans. Its impact on public health is still unknown. The present study consisted of recording the presence of the species O. microtis through the use of Sherman-type live capture traps for small mammals arranged in linear transects in the wild and intervened habitats of the Samuzabety community, where the Chapare virus was detected for the first time, this community is located in the Chapare Province of the department of Cochabamba, Bolivia. The species recorded were the rodents Oligoryzomys microtis (morphotype matogrossae), Proechimys brevicauda, Neacomys vargasllosai, Hylaeamys perenensis, and the marsupial Metachiurus nudicaudatus. The presence of the species O. microtis (morphotype matogrossae) in the community of Samuzabety is confirmed. This species is associated with forest habitats with nearby and surrounding crops. The species O. microtis has epidemiological relevance as it is the natural reservoir of the Río Mamoré Hantavirus and is currently considered a potential reservoir of the Chapare virus and other Arenaviruses.

Los roedores son organismos muy importantes dentro de los ecosistemas; sin embargo, algunas especies son consideradas como plagas porque consumen y dañan cultivos y porque son vectores, hospederos o reservorios en la trasmisión de enfermedades infecciosas emergentes. Los roedores en Bolivia están representados por 148 especies, entre las cuales Oligoryzomys microtis (Allen, 1916) es una especie de importancia en salud pública, debido a que es considerada como potencial reservorio natural del virus Chapare, el cual produce la fiebre hemorrágica Chapare, enfermedad mortal para el ser humano y con un impacto en la salud pública aún desconocido. En este estudio se registró la presencia de la especie O. microtis?/i>, mediante el uso de trampas de captura viva tipo Sherman para pequeños mamíferos dispuestas en transectos lineales, en los hábitats silvestres e intervenidos de la comunidad de Samuzabety, sitio en el que se detectó por primera vez el virus Chapare. Esta comunidad se encuentra ubicada en la Provincia Chapare del departamento de Cochabamba, Bolivia. Las especies registradas fueron los roedores Oligoryzomys microtis (morfotipo matogrossae), Proechimys brevicauda, Neacomys vargasllosai, Hylaeamys perenensis y el marsupial Metachiurus nudicaudatus. Se confirma la presencia de la especie O. microtis (morfotipo matogrossae) en la comunidad de Samuzabety, la cual se encuentra asociada con hábitats de bosques, con cultivos cercanos y a su alrededor. La especie O. microtis tiene relevancia epidemiológica al ser el reservorio natural del hantavirus Río Mamoré y al ser considerado actualmente como potencial reservorio del virus Chapare y de otros arenavirus.

Fiebre hemorrágica Chapare: una enfermedad zoonótica emergente producto de la expansión agrícola / Chapare hemorrhagic fever: an emerging zoonotic disease as a result of agricultural expansion

Chapare hemorrhagic fever is an emerging zoonotic disease caused by a Mammarenavirus, of the Arenaviridae family, called Chapare virus. Its name refers to the region in which it first appeared. This virus is transmitted through direct contact with the excreta of wild rodents that interact with humans by invading homes close to a rural area and when humans enter the jungle for various reasons such as agriculture and tourism, among others. This virus has been classified by the World Health Organization as biosafety level IV, where pathogens with the highest risk for humans are included and for which there are no vaccines available. It produces a febrile and hemorrhagic picture that leads to death two weeks after the onset of symptoms. There is no vaccine or standardized treatment to treat this disease. The bio ecological aspects of the reservoir are not known, nor are the factors that could be related to the emergency in the area. An investigation should be carried out focused mainly on knowing the circulation of the Chapare virus in the Bolivian tropics, knowing the bioecological characteristics of the reservoir to produce and contribute with reliable information for the design of future surveillance and control strategies with community participation, as well as to strengthen laboratory diagnostic capacities in health establishments in the municipality of Villa Tunari.

La fiebre hemorrágica Chapare es una enfermedad zoonótica emergente causada por un Mammarenavirus de la familia Arenaviridae, llamado virus Chapare; su nombre se debe a la región en la cual apareció por primera vez. Este virus es transmitido por medio del contacto directo con las excretas de los roedores silvestres que interactúan con el ser humano, al invadir las viviendas que se encuentran cercanas al área silvestre y cuando el hombre incursiona a la selva por diversas razones, como las actividades de agricultura o turismo, entre otras. Este virus ha sido catalogado por la Organización Mundial de la Salud como nivel de bioseguridad IV, en el cual se ubican los patógenos de mayor riesgo para el ser humano y para los cuales no existen vacunas disponibles. Produce un cuadro febril y hemorrágico que lleva al fallecimiento a las dos semanas de haber iniciado los síntomas. No existe vacuna ni tratamiento estandarizado para tratar esta enfermedad, no se conocen los aspectos bioecológicos del reservorio y tampoco los factores que podrían estar relacionados con la emergencia en la zona. Se deberá realizar una investigación enfocada principalmente en conocer la circulación del virus Chapare en la región del trópico boliviano, conocer las características bioecológicas del reservorio con el propósito de producir y aportar con información fehaciente para el diseño de futuras estrategias de vigilancia y control con participación comunitaria, así como fortalecer las capacidades de diagnóstico de laboratorio en los establecimientos de salud del municipio de Villa Tunari.

Effects and mechanism of 3,5,6,7,4'-pentamethoxyflavone forblocking arenavirus entry / 药学学报

Arenaviruses are enveloped RNA viruses, and eight members in this family are known to cause human hemorrhagic fever. Treatments for the viral hemorrhagic fever (VHF) by arenaviruses are very limited. We have identified the first flavone, tangeretin, with broad-spectrum inhibitory activities on VHF-arenaviruses infection by blocking viral entry. In this study, we evaluated thirty-four tangeretin analogues and found 3,5,6,7,4'-pentamethoxyflavone as a Lassa virus entry inhibitor, with EC50 of 5.2 µmol·L-1, by blocking the viral fusion process. The compound 3,5,6,7,4'-pentamethoxyflavone is effective on all known VHF-arenaviruses, with EC50 range of 0.84-10.2 µmol·L-1. These results suggest that 3,5,6,7,4'-pentamethoxyflavone is able to serve as a start point for discovery of arenavirus entry inhibitors from flavone natural products.

Aporé virus, a novel mammarenavirus (Bunyavirales: Arenaviridae) related to highly pathogenic virus from South America

Here, we report the complete genome sequence of the Aporé virus (Bunyavirales: Arenaviridae), obtained from a wild rodent Oligoryzomys mattogrossae captured in Mato Grosso do Sul state, Brazil. The genome of this virus showed strong similarity to highly pathogenic mammarenavirus from South America.

Rodent-borne viruses survey in rural settlers from Central Brazil

Anthropogenic environmental changes arising from settlement and agriculture include deforestation and replacement of natural vegetation by crops providing opportunities for pathogen spillover from animals to humans. This study aimed to investigate the prevalence of rodent-borne virus infections in seven rural settlements from Midwestern Brazil. Of the 466 individuals tested 12 (2.57%) were reactive for orthohantavirus and 3 (0.64%) for mammarenavirus. These rural settlers lived under unfavorable infrastructure, socioeconomic disadvantages, and unsanitary conditions, representing a risk for rodent-borne infections. Development of public policies towards the improvement of health, sanitation and awareness of rodent-borne diseases in improvised camps and settlements is imperative, in order to reduce morbidity and mortality caused by these diseases.

Establishment of evaluation system for a cell-based arenavirus entry inhibitor / 药学学报

Arenaviruses are enveloped RNA viruses. The genus mammarenavirus contains nine members that are known to be human pathogens, and eight of them cause human hemorrhagic fever. Lassa hemorrhagic fever, caused by Lassa virus (LASV) infection, is the most prevalent arenavirus hemorrhagic fever with potential to cause major epidemics. LASV belongs to category A agents, and biosafety level-4 (BSL-4) facility is required for live virus experiments. Currently there are few specific treatments available for arenavirus diseases. Here, we established efficient cell-based pseudovirus infection models using an HIV-1 core (pNL4-3.Luc.R-E-) packed with arenavirus glycoproteins. Nine recombinant arenaviruses (arenavirus-GP/HIV-luc) were generated, and 17 cell lines were tested for susceptibilities to these viruses. These pseudovirus infection models were further validated by known arenavirus entry inhibitors. The models are safe and specific to pseudovirus infection, which are readily used for pharmacodynamic evaluation of arenavirus entry inhibitors in BSL-2 laboratory. The models will facilitate screening of the anti-arenavirus drugs and vaccines.

Doença do corpúsculo de inclusão e espondilite por Salmonella sp. em uma Boa constrictor constrictor / Inclusion body disease and spondilitis by Salmonella sp. in a Boa constrictor constrictor

Doença do corpúsculo de inclusão (IBD) é uma enfermidade caracterizada por corpúsculos intracitoplasmáticos em diversos tecidos, principalmente no sistema nervoso central, responsável pelos principais sinais clínicos atribuídos à doença que acomete Boas e Phytons de cativeiro; essa enfermidade tem sido uma preocupação mundial devido à alta morbidade e mortalidade. O diagnóstico é feito pela visualização dos corpúsculos causados por um Arenavírus modificado. Salmonella sp. pertence à microflora de animais de sangue frio e quente, e é um patógeno oportunista que pode causar quadros gastrointestinais ou septicêmicos. Em répteis a Salmonella sp. é a bactéria com maior frequência de citações em espondilites e osteomielites. Relata-se um caso de uma jiboia (Boa constrictor constrictor) que apresentava restrição de movimento e múltiplos granulomas dorsais nas vértebras; à radiografia evidenciaram-se regiões fraturadas. Após meses de tratamentos sem melhora clínica e o aparecimento de novas lesões o animal ficou prostrado, anoréxico, caquético e desenvolveu opistótono; optou-se pela eutanásia. À necropsia verificaram-se, nas vértebras, múltiplos focos dorsais com aumento de volume que variava de 1,7cm à 3,8cm. Ao corte as vértebras eram deformadas e exibiam conteúdo caseoso focal próximo ao canal medular, este foi coletado para microbiologia onde se identificou Salmonella sp. À microscopia as vértebras tinham um infiltrado inflamatório multifocal moderado de macrófagos e heterofilos. Algumas áreas possuíam grande quantidade de granulomas com calcificação central e inúmeras células gigantes; outros mostravam áreas de osteomalácia e fibrose. Em raros focos havia fratura do corpo vertebral e compressão da medula espinhal com leve infiltrado inflamatório invadindo o canal medular. No pulmão, principalmente no epitélio brônquico, por vezes até dentro de linfócitos do tecido linfoide bronco-associado, no intestino, fígado, vesícula biliar, nos rins e no encéfalo foram encontradas diversas estruturas eosinofílicas intracitoplasmáticas arredondadas que variavam de 1 a 10 µm. Essas estruturas acompanhavam ou não inflamações mononucleares. Os achados são compatíveis com IBD e espondilite por salmonelose. A IBD é uma enfermidade frequente em serpentes de cativeiro, de importância mundial, que provavelmente é subdiagnosticada no Brasil. Essa doença causa imunossupressão que favorece ao desenvolvimento de outras enfermidades, e é tipicamente associada a outras doenças como a espondilite encontrada no caso.(AU)

Inclusion Body Disease (IBD) is a disorder characterized by intracytoplasmic corpuscles in different tissues, mainly in the CNS, wich is responsible for the major neurological signs attributable to this disease. It affects Boas and Phytons in captivity and have been a global concern due to the high morbidity and mortality. The diagnosis is made by visualization of corpuscles caused by a modified Arenaviruses. Salmonella sp. belongs to microflora of cold and warm-blooded animals; it is an opportunistic pathogen that can causes gastrointestinal or septic disorders. In reptiles, Salmonella sp. is the bacteria most frequently quotes in spondylitis and osteomyelitis. This article describes a boa constrictor (Boa constrictor constrictor) that had restriction of movement and multiple granulomas in the dorsal vertebrae, the shadowgraph showed up fractured regions. After months of treatment without clinical improvement and the emergence of new injuries, the animal started to get prostrate, anorexic, cachectic and developed opisthotonos. It was opted for euthanasia. At necropsy it was found in multiple spots swelling of the dorsal vertebrae that ranging from mild to moderate. At the cutting vertebrae it was visible deformed and showed focal caseous content near the spinal cord, this was collected for microbiology where it was identified Salmonella sp. At microscopic evaluation the vertebrae had one to multifocal moderate inflammatory infiltrate of macrophages and heterophils. Some areas had lots of granulomas with central calcification and numerous giant cells. Other vertebras showed areas of osteomalácea and fibrosis. Rare focus had vertebral body fracture and spinal cord compression with mild infiltration entering the spinal cord canal. In the lung, especially in the bronchial epithelium, sometimes even within lymphocytes in bronchial-associated lymphoid tissue, in the intestine, liver, gall bladder, kidney and brain were found various structures of eosinophilic intracytoplasmic rounded ranging between 1 and 10 micrometers. These structures accompanied or not mononuclear inflammation. These findings are consistent with IBD and spondylitis due to salmonellosis. The IBD is a common disease in captive snakes, of world importance, is probably underdiagnosed in Brazil. This disease causes immunosuppression favoring the development of other affections, and is typically associated with other diseases such as spondylitis found in the case.(AU)

Primera evidencia de infección por el virus de la coriomeningitis linfocítica (arenavirus) en roedores Mus musculus capturados en la zona urbana del municipio de Sincelejo, Sucre, Colombia / First evidence of lymphocytic choriomeningitis virus (Arenavirus) infection in Mus musculus rodents captured in the urban area of the municipality of Sincelejo, Sucre, Colombia

Resumen Introducción. El virus de la coriomeningitis linfocítica es un arenavirus del Viejo Mundo que se hospeda en el ratón casero (Mus musculus), y puede causar infecciones congénitas, hidrocefalia, coriorretinitis y falla orgánica múltiple en pacientes receptores de trasplantes. En Colombia aún no se ha reportado la enfermedad mediante diagnóstico clínico, pero en estudios serológicos se ha detectado la infección por el virus Pichindé en roedores en los departamentos del Cauca y Valle del Cauca, y por el virus Guanarito, en roedores en Córdoba. Objetivo. Detectar el virus de la coriomeningitis linfocítica en M. musculus en el municipio de Sincelejo. Materiales y métodos. Se evaluaron 80 muestras de plasma mediante la prueba ELISA usando antígeno del virus de la coriomeningitis linfocítica. Además, se empleó la reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) anidada en muestras de animales seropositivos y seronegativos para la detección del segmento S. Resultados. Se encontró una seroprevalencia de 10% (8/80) y se detectó el genoma viral en 16 muestras de cerebro; el alineamiento (en la Basic Local Alignment Search Tool, BLAST) y el análisis filogenético (mediante el programa MrBayes, versión 3.2.2) confirmaron que correspondía al virus de la coriomeningitis linfocítica. Conclusión. Los resultados indicaron que la infección por el virus de la coriomeningitis linfocítica en humanos podría ocurrir en el área urbana de Sincelejo, aunque hasta la fecha no se hayan reportado casos.

Abstract Introduction: The lymphocytic choriomeningitis virus is an Old World arenavirus that infects Mus musculus, and can cause congenital hydrocephalus, chorioretinitis and multisystemic failure in transplant human recipients. Although the disease has not been clinically diagnosed in Colombia yet, there have been reports of infection with the Pichindé virus in rodents from Cauca and Valle del Cauca departments, and with the Guanarito virus in rodents from Córdoba department. Objective: To identify the lymphocytic choriomeningitis virus from Mus musculus captured in the municipality of Sincelejo. Materials and methods: We evaluated 80 samples of plasma by ELISA using antigen from lymphocytic choriomeningitis virus. Additionally, a nested RT-PCR was performed to seropositive and seronegative samples for the S-segment. Results: We found a 10% seroprevalence (8/80) and the viral genome was detected in 16 brain samples; the alignment (BLAST) and the phylogenetic analysis (MrBayes, version 3.2.2) confirmed the presence of the lymphocytic choriomeningitis virus. Conclusion: The results indicated that human infection with the lymphocytic choriomeningitis virus in humans could occur in the urban area of Sincelejo, although no cases have been reported so far.

Evidencia serológica retrospectiva de infecciones por Leptospira spp, dengue, hantavirus y arenavirus en indígenas Emberá-Katío, Colombia / Serological evidence of Leptospira spp, dengue, hantavirus and arenavirus infection in Embera-Katío indigenous population, Colombia

We have developed a study in the Embera-Katío indigenous community and we found that the seropositivity for IgG antibodies to Leptospira spp. was 18.1%; to dengue was 61.1%; to arenavirus was 3.1% and to hantavirus was 1.5%. We conclude that this indigenous community live in conditions that promote the reemerging and emerging, infections.

Los nuevos escenarios de transmisión de la fiebre hemorrágica Argentina desde la introducción de la vacuna a virus Junín vivo atenuado (Candid#1): una experiencia en trabajadores golondrinas / New transmission scenarios of the Argentine hemorrhagic fever since the introduction of the live attenuated Junin virus vaccine (Candid #1): an experience in migrant workers

La fiebre hemorrágica Argentina (FHA) es una enfermedad viral aguda grave causada por el virus Junín, de la familia Arenaviridae. El área endémica de la FHA coincide geográficamente con el mayor complejo agroindustrial cerealero de exportación del Argentina. Desde la implementación de la vacunación con Candid#1, se logró una importante reducción de la incidencia y se modificaron los patrones de riesgo. Un estudio previo permitió caracterizar estos cambios e identificar tres escenarios de transmisión: clásico, emergente-reemergente y viajero. Dentro de este último escenario se incluyen los trabajadores migrantes estacionales que se desplazan cada año, principalmente desde la provincia de Santiago del Estero, al área endémica para trabajar en el despanojado de maíz. Con el objetivo de brindar protección a este grupo de trabajadores se inició una campaña de prevención que incluyó: capacitación de personal de salud de esta provincia, educación para la salud e inmunización con vacuna Candid#1. Se vacunaron 3021 trabajadores. Previo a la vacunación, se tomaron muestras de suero en un grupo de 104 voluntarios. Se realizó la detección de anticuerpos neutralizantes específicos para virus Junín en el total de las mismas y 6 (5,76%) arrojaron resultado positivo. El inesperado hallazgo de un elevado porcentaje de trabajadores con anticuerpos, nos sugiere la necesidad de valorar varias hipótesis: a) que el resultado sea producto de un muestreo no probabilístico; b) que podría tratarse de personas que enfermaron en viajes previos, c) o que se vacunaron en viajes previos; d) considerar esta región como un escenario emergente.

The Argentine hemorrhagic fever (AHF) is a severe acute viral disease caused by the Junin virus of the Arenaviridae family. The AHF endemic area coincides geographically with the largest grain export agro-industrial complex of the country [Argentina]. Since the implementation of vaccination with the Candid #1 vaccine, a significant reduction in incidence was achieved and risk patterns were modified. A previous study allowed characterizing these changes and identifying three transmission scenarios: classic, emergent-reemergent, and traveler. The latter scenario includes seasonal migrant workers who move each year, mainly from the province of Santiago del Estero, the endemic area to work in the detasseling of maize. With the objective of protecting this group of workers, a prevention campaign was initiated which included: capacity building of health personnel in the province, health education, and immunization with the vaccine Candid #1. 3,021 workers were vaccinated. Prior to vaccination, serum samples were taken from a group of 104 volunteers. Tests for neutralizing antibodies specific to the Junin virus were performed and 6 (5.76%) tested positive. The unexpected finding of a high percentage of workers with antibodies suggests the need to evaluate several hypotheses: a) that the result is the product of non-probabilistic sampling; b) that it could be people who fell ill in previous travels, c) or who were vaccinated in previous travels; or d) consider this region as an emerging scenario.

Detection and phylogenetic analysis of arenavi rus carried by wild rodents in Ningbo,China / 中国人兽共患病学报

To detect and phylogeneticaly analyze arenavirus carried by wild rodents in Ningbo ,China ,two pairs of degener‐ate‐primers were designed to amplify the S and L gene of arenavirus ,and then RT‐PCR was applied to detect arenavirus carried by rodents which captured from Ningbo port area .All 73 rodents samples were detected ,of which 12 Rattus norvegicus were positive ,an arenavirus virus strain named DX1401 were separated .The S gene amplified products of DX1401 was about 413 bp ,and the L gene was 1 204 bp .The phylogenetic analysis of S segments showed that DX1401 strain was in one branch of phylogenetic tree with Mobala virus strain ACAR3080 .The genetic distance to Mobala virus strain ACAR3080 was the closest , with the value of 0 .467 ;the phylogenetic analysis of L segments showed that DX1401 strain were in one group of phylogenetic tree with Lassa virus strain Josiah ,NL ,Z148 ,Bamba‐R114 ,Soromba‐R ,Nig08‐A37 ,Nig08‐A47 ,Mobala virus strain ACAR3080 ,Morogoro virus strain 13017/2004 ,Mopeia virus strain Mozambique ,and AN 21366‐BNI .The genetic distance to Mobala virus strain ACAR3080 was the closest ,with the value of 6 .953 .In conclusion ,the study confirmed the existence of arenavirus popular in wild rodents in Ningbo ,China .

Analyses of Entry Mechanisms of Novel Emerging Viruses Using Pseudotype VSV System

Emerging infectious diseases include newly identified diseases caused by previously unknown organisms or diseases found in new and expanding geographic areas. Viruses capable of causing clinical disease associated with fever and bleeding are referred to as viral hemorrhagic fevers (VHFs). Arenaviruses and Bunyaviruses, both belonging to families classified as VHFs are considered major etiologies of hemorrhagic fevers caused by emerging viruses; having significant clinical and public health impact. Because these viruses are categorized as Biosafety Level (BSL) 3 and 4 pathogens, restricting their use, biological studies including therapeutic drug and vaccine development have been impeded. Due to these restrictions and the difficulties in handling such live viruses, pseudotype viruses bearing envelope proteins of VHF viruses have been developed using vesicular stomatitis virus (VSV) as a surrogate system. Here, we report the successful developments of two pseudotype VSV systems; bearing the envelope proteins of Lujo virus and severe fever with thrombocytopenia syndrome (SFTS) virus, both recently identified viruses of the family Arenaviridae and Bunyaviridae, respectively. My presentation will summarize the characterization of the envelope proteins of Lujo virus including its cellular receptor use and cell entry mechanisms. In addition, I will also present a brief introduction of SFTS reported in Japan and the diagnostic studies in progress using these newly pseudotype VSV system.

Analyses of entry mechanisms of novel emerging viruses using pseudotype VSV system

Emerging infectious diseases include newly identified diseases caused by previously unknown organisms or diseases found in new and expanding geographic areas. Viruses capable of causing clinical disease associated with fever and bleeding are referred to as viral hemorrhagic fevers (VHFs). Arenaviruses and Bunyaviruses, both belonging to families classified as VHFs are considered major etiologies of hemorrhagic fevers caused by emerging viruses; having significant clinical and public health impact. Because these viruses are categorized as Biosafety Level (BSL) 3 and 4 pathogens, restricting their use, biological studies including therapeutic drug and vaccine development have been impeded. Due to these restrictions and the difficulties in handling such live viruses, pseudotype viruses bearing envelope proteins of VHF viruses have been developed using vesicular stomatitis virus (VSV) as a surrogate system. Here, we report the successful developments of two pseudotype VSV systems; bearing the envelope proteins of Lujo virus and severe fever with thrombocytopenia syndrome (SFTS) virus, both recently identified viruses of the family Arenaviridae and Bunyaviridae, respectively. My presentation will summarize the characterization of the envelope proteins of Lujo virus including its cellular receptor use and cell entry mechanisms. In addition, I will also present a brief introduction of SFTS reported in Japan and the diagnostic studies in progress using these newly pseudotype VSV system.

Fiebres hemorrágicas por Arenavirus en Latinoamérica / Hemorrhagic fever Arenaviruses in Latin America

Las fiebres hemorrágicas virales producidas por Arenavirus incluyen a los virus endémicos en África (Lassa) y el virus de la coriomeningitis linfocítica (LCMV), de distribución mundial, y los Arenavirus del Nuevo Mundo o Complejo Tacaribe, que incluye a los virus endémicos en las Américas (Junín, Machupo, Guanarito, Sabiá, Pichinde, entre otros). Los huéspedes naturales son los roedores y la infección en humanos se produce por el contacto con la orina y excretas. Las manifestaciones clínicas inicialmente son indistinguibles de otras fiebres hemorrágicas producidas por bacterias, parásitos y otros virus, constituyéndose esto en un problema de salud pública, por lo que se requiere realizar el diagnóstico diferencial utilizando técnicas serológicas y moleculares.

Viral hemorrhagic fevers caused by Arenaviruses include endemic viruses in Africa (Lassa fever) and lymphocytic choriomeningitis virus (LCMV) of worldwide distribution, and the New World Arenavirus or Tacaribe Complex, which includes endemic viruses in the Americas (Junin, Machupo, Guanarito, Sabia, Pichinde, among others). The natural hosts are rodents and human infection occurs through contact with urine and excrements. The clinical manifestations are initially indistinguishable from other viral hemorrhagic fevers caused by bacteria, parasites and other viruses, constituting a public health problem. So it requires a differential diagnosis using serological and molecular techniques..

Standardization of an ELISA test using a recombinant nucleoprotein from the Junin virus as the antigen and serological screening for arenavirus among the population of Nova Xavantina, State of Mato Grosso / Padronização de um teste de ELISA utilizando a nucleoproteína recombinante de vírus Junin como antígeno e triagem sorológica para Arenavírus na população de Nova Xavantina, Estado do Mato Grosso

INTRODUCTION: Arenavirus hemorrhagic fever is a severe emerging disease. METHODS: Considering that the levels of antibodies against arenavirus in the Brazilian population are completely unknown, we have standardized an ELISA test for detecting IgG antibodies using a recombinant nucleoprotein from the Junin virus as the antigen. This protein was obtained by inserting the gene of the Junin virus nucleoprotein into the genome of Autographa californica nucleopolyhedrovirus, using the Bac-to-Bac baculovirus expression system. This recombinant baculovirus was used to infect S. frugiperda cells (SF9). RESULTS: The infection resulted in synthesis of high concentrations of recombinant protein. This protein was detected on 12.5 percent polyacrylamide gel and by means of Western blot. Using the standardized ELISA test, 343 samples from the population of Nova Xavantina were analyzed. We observed that 1.4 percent of the serum samples (five samples) presented antibody titers against arenavirus. CONCLUSIONS: These results show the population studied may present exposure to arenavirus infection.

INTRODUÇÃO: A febre hemorrágica por Arenavirus é uma severa doença emergente. MÉTODOS: Considerando que os níveis de anticorpos contra Arenavirus na população brasileira é totalmente desconhecido, nos padronizamos um teste de ELISA para detecção de anticorpos IgG usando uma nucleoproteína recombinante do vírus Junin como antígeno. Esta proteína foi obtida pela inserção do gene da nucleoproteína do vírus Junin no genoma do vírus Autographa californica nucleopolyhedrovirus, utilizando o sistema de expressão em Baculovírus, Bac-To-Bac. Este baculovirus recombinante foi utilizado para infecção de células de S. frugiperda (Sf9). RESULTADOS: A infecção resultou na produção de altas concentrações de proteína recombinante. Esta proteína foi detectada em gel de poliacrilamida 12,5 por cento, e em Western blot. Utilizando o teste de ELISA padronizado, foram analizadas 343 amostras provenientes da população de Nova Xavantina. Observamos que 1,4 por cento dos soros (5 amostras) apresentavam títulos de anticorpos contra arenavírus. CONCLUSÕES: Estes resultados sugerem que a população estudada pode estar sendo exposta a infecções por arenavírus.

Contribution of the murine and primate models to thestudy of arenaviral diseases and hemorrhagic fevers / Contribución de los modelos murino y primate al estudio de las enfermedades porarenavirus y fiebres hemorrágicas / Contribuição dos modelos murinos e primatas ao estudo de doenças por arenavirus efebre hemorrágica

This manuscript is an inedited part of my PhD dissertation, based on historical and recent findingson animal models, that was presented as part of the requirements to fulfill the conditions to become aphilosophical doctor on Veterinary Sciences at the University of Wisconsin on October of 2003.The currentmini-review written on a free-version style, underlines some of the cornerstones of immunology as ascience, understood thanks to the use of the Lymphocytic Choriomeningitis virus (LCMV) experimentallyand naturally infected mouse model. It should suffice to say that there have been two Nobel prices ofMedicine for discoveries made through the employment of this animal model, in order to recognize theright importance to it. In addition, several laboratories, Dr. Salvato´s among them, have also employed theLCMV-infected Rhesus monkey model as a tool to unravel the mysteries of arenaviral hemorrhagic fever,and particularly the physiopathology of Lassa disease in humans. Here I show some of the knowledgegenerated through the study of both animal infections.

El siguiente manuscrito, es un capítulo inédito de mi tesis doctoral, basado en hallazgos históricos yrecientes sobre modelos animales, que fue presentado como parte de los requisitos para obtener el títulode Ph.D. en Ciencias veterinarias en la Universidad de Wisconsin, en Octubre de 2003.La actual minirevisiónescrita en estilo de versión libre, subraya algunas de las piedras angulares de la inmunología comociencia, entendidas gracias al uso del modelo murino infectado natural y experimentalmente con el virusde Coriomeningitis Linfocítica (LCMV). Sería suficiente mencionar que han existido dos premios Nóbelde Medicina por descubrimientos realizados a través del empleo de este modelo animal, para reconocer lareal importancia del mismo. Adicionalmente, varios laboratorios, el de la Dra. Salvato entre ellos, tambiénhan empleado el modelo del mono Rhesus como un instrumento para desvelar los misterios de las fiebreshemorrágicas por arenavirus, y particularmente la fisiopatología de la enfermedad de Lassa en humanos.Aquí yo muestro alo del conocimiento generado a través del estudio de ambas infecciones animales.

O seguinte manuscrito é um capítulo inédito da minha tese doutoral, baseado em casos históricose recentes sobre modelos animais, que foram apresentados na defesa da tese de Ph.D. em CiênciasVeterinárias da Universidade de Wisconsin, em outubro de 2003. A atual mini revisão escrita em estilode versão livre, enfatiza em algumas pedras angulares da inmunologìa como ciência. Graças ao usodo modelo murino infectado natural e experimentalmente com o vírus da Coriomeningitis Linfocítica(LCMV). Seria suficiente mencionar que foram outorgados dois prêmios Nobel de Medicina pelosdescobrimentos realizados a través do uso deste modelo, para reconhecer a real importância do mesmo.Adicionalmente, vários laboratórios, entre eles o da Dra. Salvato, tem utilizado o modelo macaco Rhesuscomo um instrumento para desvelar os mistérios das febres hemorrágicas por arenavirus, e particularmentea fisiologia e patologia da doença de Lassa em humanos. Aqui eu indico algo do conhecimento gerado através do estudo das duas infecções animais.