RESUMEN
Orthohantaviruses are diverse zoonotic RNA viruses. Small mammals, such as mice and rats are common chronic, asymptomatic hosts that transmit the virus through their feces and urine. In North America, hantavirus infection primarily causes hantavirus cardiopulmonary syndrome (HCPS), which has a mortality rate of nearly 36%. In the United States of America, New Mexico (NM) is leading the nation in the number of HCPS-reported cases (N = 129). However, no reported cases of HCPS have occurred within eastern NM. In this study, we assessed the prevalence of Sin Nombre virus (SNV) in rodent assemblages across eastern NM, using RT-qPCR. We screened for potential rodent hosts in the region, as well as identified areas that may pose significant infection risk to humans. We captured and collected blood and lung tissues from 738 rodents belonging to 23 species. 167 individuals from 16 different species were positive for SNV RNA by RT-qPCR, including 6 species unreported in the literature: Onychomys leucogaster (Northern grasshopper mouse), Dipodomys merriami (Merriam's kangaroo rat), Dipodomys ordii (Ord's kangaroo rat), Dipodomys spectabilis (Banner-tailed kangaroo rat), Perognathus flavus (Silky pocket mouse), and Chaetodipus hispidus (Hispid pocket mouse). The infection rates did not differ between sexes or rodent families (i.e., Cricetidae vs. Heteromyidae). Generalized linear model showed that disturbed habitat types positively influenced the prevalence of SNV at sites of survey. Overall, the results of this study indicate that many rodent species in east New Mexico have the potential to maintain SNV in the environment, but further research is needed to assess species specific infectivity mechanisms and potential risk to humans.
Asunto(s)
Infecciones por Hantavirus , Síndrome Pulmonar por Hantavirus , Orthohantavirus , Virus Sin Nombre , Humanos , Animales , Ratones , Roedores , Dipodomys , Virus Sin Nombre/genética , New Mexico/epidemiología , Prevalencia , Infecciones por Hantavirus/epidemiología , Infecciones por Hantavirus/veterinaria , Orthohantavirus/genética , Arvicolinae , Síndrome Pulmonar por Hantavirus/epidemiología , Síndrome Pulmonar por Hantavirus/veterinariaRESUMEN
The Bunyavirales order is a large and diverse group of segmented negative-strand RNA viruses. Several virus families within this order contain important human pathogens, including Sin Nombre virus (SNV) of the Hantaviridae. Despite the high epidemic potential of bunyaviruses, specific medical countermeasures such as vaccines or antivirals are missing. The multifunctional ~250 kDa L protein of hantaviruses, amongst other functional domains, harbors the RNA-dependent RNA polymerase (RdRp) and an endonuclease and catalyzes transcription as well as replication of the viral RNA genome, making it a promising therapeutic target. The development of inhibitors targeting these key processes requires a profound understanding of the catalytic mechanisms. Here, we established expression and purification protocols of the full-length SNV L protein bearing the endonuclease mutation K124A. We applied different biochemical in vitro assays to provide an extensive characterization of the different enzymatic functions as well as the capacity of the hantavirus L protein to interact with the viral RNA. By using single-particle cryo-EM, we obtained a 3D model including the L protein core region containing the RdRp, in complex with the 5' promoter RNA. This first high-resolution model of a New World hantavirus L protein shows striking similarity to related bunyavirus L proteins. The interaction of the L protein with the 5' RNA observed in the structural model confirms our hypothesis of protein-RNA binding based on our biochemical data. Taken together, this study provides an excellent basis for future structural and functional studies on the hantavirus L protein and for the development of antiviral compounds.
Asunto(s)
Bunyaviridae , Orthohantavirus , Virus ARN , Virus Sin Nombre , Humanos , Virus Sin Nombre/genética , Virus Sin Nombre/metabolismo , Orthohantavirus/genética , ARN Polimerasa Dependiente del ARN/genética , Bunyaviridae/metabolismo , ARN Viral/genética , Virus ARN/genética , Endonucleasas/genética , Endonucleasas/metabolismoRESUMEN
Rodent-borne hantaviruses are prevalent worldwide and upon spillover to human populations, cause severe disease for which no specific treatment is available. A potent antibody response is key for recovery from hantavirus infection. Here we study a highly neutralizing human monoclonal antibody, termed SNV-42, which was derived from a memory B cell isolated from an individual with previous Sin Nombre virus (SNV) infection. Crystallographic analysis demonstrates that SNV-42 targets the Gn subcomponent of the tetrameric (Gn-Gc)4 glycoprotein assembly that is relevant for viral entry. Integration of our 1.8 Å structure with the (Gn-Gc)4 ultrastructure arrangement indicates that SNV-42 targets the membrane-distal region of the virus envelope. Comparison of the SNV-42 paratope encoding variable genes with inferred germline gene segments reveals high sequence conservation, suggesting that germline-encoded antibodies inhibit SNV. Furthermore, mechanistic assays reveal that SNV-42 interferes with both receptor recognition and fusion during host-cell entry. This work provides a molecular-level blueprint for understanding the human neutralizing antibody response to hantavirus infection.
Asunto(s)
Infecciones por Hantavirus , Virus Sin Nombre , Humanos , Virus Sin Nombre/fisiología , Anticuerpos Monoclonales , Anticuerpos Neutralizantes , GlicoproteínasRESUMEN
We demonstrate that 6 distinct Peromyscus rodent species are permissive to experimental infection with Sin Nombre orthohantavirus (SNV). Viral RNA and SNV antibodies were detected in members of all 6 species. P. leucopus mice demonstrated markedly higher viral and antibody titers than P. maniculatus mice, the established primary hosts for SNV.
Asunto(s)
Síndrome Pulmonar por Hantavirus , Enfermedades de los Roedores , Virus Sin Nombre , Animales , Anticuerpos Antivirales , Peromyscus , ARN Viral , Enfermedades de los Roedores/epidemiología , Roedores , Virus Sin Nombre/genéticaRESUMEN
Orthohantaviruses are negative-stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. Old World orthohantaviruses are primarily located throughout Europe and Asia, causing hemorrhagic fever with renal syndrome, and New World orthohantaviruses are found in North, Central, and South America, causing hantavirus cardiopulmonary syndrome (HCPS). In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of HCPS with a fatality rate of ~36%. The primary SNV host reservoir is thought to be the North American deer mouse, Peromyscus maniculatus. However, it has been shown that other species of Peromyscus can carry different orthohantaviruses. Few studies have systemically surveyed which orthohantaviruses may exist in wild-caught rodents or monitored spillover events into additional rodent reservoirs. A method for the rapid detection of orthohantaviruses is needed to screen large collections of rodent samples. Here, we report a pan-orthohantavirus, two-step reverse-transcription quantitative real-time PCR (RT-qPCR) tool designed to detect both Old and New World pathogenic orthohantavirus sequences of the S segment of the genome and validated them using plasmids and authentic viruses. We then performed a screening of wild-caught rodents and identified orthohantaviruses in lung tissue, and we confirmed the findings by Sanger sequencing. Furthermore, we identified new rodent reservoirs that have not been previously reported as orthohantavirus carriers. This novel tool can be used for the efficient and rapid detection of various orthohantaviruses, while uncovering potential new orthohantaviruses and host reservoirs that may otherwise go undetected.
Asunto(s)
Infecciones por Hantavirus , Síndrome Pulmonar por Hantavirus , Orthohantavirus , Enfermedades de los Roedores , Virus Sin Nombre , Animales , Reservorios de Enfermedades , Orthohantavirus/genética , Infecciones por Hantavirus/diagnóstico , Infecciones por Hantavirus/epidemiología , Infecciones por Hantavirus/veterinaria , Peromyscus , Enfermedades de los Roedores/epidemiología , RoedoresRESUMEN
Sin Nombre orthohantavirus (SNV), a negative-sense, single-stranded RNA virus that is carried and transmitted by the North American deer mouse Peromyscus maniculatus, can cause infection in humans through inhalation of aerosolized excreta from infected rodents. This infection can lead to hantavirus cardiopulmonary syndrome (HCPS), which has an â¼36% case-fatality rate. We used reverse transcriptase quantitative PCR (RT-qPCR) to confirm SNV infection in a patient and identified SNV in lung tissues in wild-caught rodents from potential sites of exposure. Using viral whole-genome sequencing (WGS), we identified the likely site of transmission and discovered SNV in multiple rodent species not previously known to carry the virus. Here, we report, for the first time, the use of SNV WGS to pinpoint a likely site of human infection and identify SNV simultaneously in multiple rodent species in an area of known host-to-human transmission. These results will impact epidemiology and infection control for hantaviruses by tracing zoonotic transmission and investigating possible novel host reservoirs. IMPORTANCE Orthohantaviruses cause severe disease in humans and can be lethal in up to 40% of cases. Sin Nombre orthohantavirus (SNV) is the main cause of hantavirus disease in North America. In this study, we sequenced SNV from an infected patient and wild-caught rodents to trace the location of infection. We also discovered SNV in rodent species not previously known to carry SNV. These studies demonstrate for the first time the use of virus sequencing to trace the transmission of SNV and describe infection in novel rodent species.
Asunto(s)
Reservorios de Enfermedades/virología , Síndrome Pulmonar por Hantavirus/transmisión , Síndrome Pulmonar por Hantavirus/veterinaria , Síndrome Pulmonar por Hantavirus/virología , Enfermedades de los Roedores/transmisión , Enfermedades de los Roedores/virología , Roedores/virología , Virus Sin Nombre , Animales , Anticuerpos Antivirales , Secuencia de Bases , Femenino , Orthohantavirus/genética , Infecciones por Hantavirus/genética , Infecciones por Hantavirus/transmisión , Infecciones por Hantavirus/veterinaria , Síndrome Pulmonar por Hantavirus/epidemiología , Humanos , Pulmón , Masculino , Ratones , América del Norte , Peromyscus/virología , Prevalencia , ARN Viral/genética , Enfermedades de los Roedores/epidemiología , Virus Sin Nombre/genética , Población Blanca , Secuenciación Completa del GenomaRESUMEN
Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We measured viral load, levels of various cytokines, urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1). We found significantly elevated levels of proinflammatory cytokines and PAI-1 in five end-stage cases. There was no difference between the expression of active uPA in survivors' and decedents' cases. However, total uPA in decedents' cases was significantly higher compared to survivors'. In some end-stage cases, uPA was refractory to PAI-1 inhibition as measured by zymography, where uPA and PAI-1 were strongly correlated to lymphocyte counts and IFN-γ. We also found bacterial co-infection influencing the etiology and outcome of immune response in two cases. Unsupervised Principal Component Analysis and hierarchical cluster analyses resolved separate waves of correlated immune mediators expressed in one case patient due to a sequential co-infection of bacteria and SNV. Overall, a robust proinflammatory immune response, characterized by an imbalance in T helper 17 (Th17) and regulatory T-cells (Treg) subsets, was correlated with dysregulated inflammation and mortality. Our sample size is small; however, the core differences correlated to survivors and end-stage HCPS are instructive.
Asunto(s)
Citocinas/genética , Citocinas/inmunología , Infecciones por Hantavirus/complicaciones , Infecciones por Hantavirus/inmunología , Síndrome Pulmonar por Hantavirus/inmunología , Plasminógeno/genética , Virus Sin Nombre/patogenicidad , Adolescente , Adulto , Coinfección/complicaciones , Coinfección/microbiología , Coinfección/virología , Citocinas/clasificación , Femenino , Infecciones por Hantavirus/fisiopatología , Síndrome Pulmonar por Hantavirus/fisiopatología , Humanos , Inflamación/inmunología , Inflamación/virología , Estudios Longitudinales , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Plasminógeno/análisis , Plasminógeno/inmunología , Estudios Retrospectivos , Virus Sin Nombre/inmunología , Adulto JovenRESUMEN
The naming of pathogens and their associated syndromes is a thorny process which unfolds in a complex geopolitical environment. This brief piece offers perspective on the multitude of forces that shape the name of a pathogen and summarizes the story of Sin Nombre Virus, with some reference to the ongoing saga of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A monopoly on names and circulating monikers rarely exists, and certain communities become disproportionately impacted by misunderstandings or stigmatization. By acknowledging these processes, we can better serve as allies to affected communities dealing with both pandemic and prejudice.
Asunto(s)
Terminología como Asunto , COVID-19/virología , Humanos , SARS-CoV-2/fisiología , Virus Sin Nombre/fisiología , Organización Mundial de la SaludRESUMEN
Sin Nombre virus (SNV) is a zoonotic virus that is highly pathogenic to humans. The deer mouse, Peromyscus maniculatus, is the primary host of SNV, and SNV prevalence in P. maniculatus is an important indicator of human disease risk. Because the California Channel Islands contain permanent human settlements, receive hundreds of thousands of visitors each year, and can have extremely high densities of P. maniculatus, surveillance for SNV in island P. maniculatus is important for understanding the human risk of zoonotic disease. Despite the importance of surveillance on these heavily utilized islands, SNV prevalence (i.e. the proportion of P. maniculatus that test positive to antibodies to SNV) has not been examined in the last 13-27 years. We present data on 1,610 mice sampled for four consecutive years (2014-2017) on five of the California Channel Islands: East Anacapa, Santa Barbara, Santa Catalina, San Nicolas, and San Clemente. Despite historical data indicating SNV-positive mice on San Clemente and Santa Catalina, we detected no SNV-positive mice on these islands, suggesting very low prevalence or possible loss of SNV. Islands historically free of SNV (East Anacapa, Santa Barbara, and San Nicolas) remained free of SNV, suggesting that rates of pathogen introduction from other islands and/or the mainland are low. Although continued surveillance is warranted to determine whether SNV establishes on these islands, our work helps inform current human disease risk in these locations and suggests that SNV prevalence on these islands is currently very low.
Asunto(s)
Síndrome Pulmonar por Hantavirus , Enfermedades de los Roedores , Virus Sin Nombre , Animales , Anticuerpos Antivirales , Islas Anglonormandas , Síndrome Pulmonar por Hantavirus/epidemiología , Síndrome Pulmonar por Hantavirus/veterinaria , Ratones , Peromyscus , Prevalencia , Enfermedades de los Roedores/epidemiologíaRESUMEN
Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, the impacts of such interactions on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce nematode infection and measured the effects on both nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary reservoir (Peromyscus spp.). Treatment significantly reduced nematode infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both nematodes and SNV were in better condition and survived up to four times longer than uninfected or singly infected mice. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.
Asunto(s)
Nematodos , Parásitos , Enfermedades de los Roedores , Virus Sin Nombre , Animales , Anticuerpos Antivirales , Masculino , Ratones , Peromyscus , Enfermedades de los Roedores/epidemiología , Roedores , Estudios SeroepidemiológicosRESUMEN
Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by Sin Nombre virus in North America (SNV). As of January 1, 2020, SNV has caused 143 laboratory-confirmed cases of HCPS in Canada. We review critical aspects of SNV virus epidemiology and the ecology, biology, and genetics of HCPS in Canada.
Asunto(s)
Infecciones por Hantavirus , Síndrome Pulmonar por Hantavirus , Orthohantavirus , Virus Sin Nombre , Canadá/epidemiología , Orthohantavirus/genética , Infecciones por Hantavirus/epidemiología , Síndrome Pulmonar por Hantavirus/diagnóstico , Síndrome Pulmonar por Hantavirus/epidemiología , Humanos , América del NorteRESUMEN
BACKGROUND: Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%-50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors. METHODOLOGY AND MAIN FINDINGS: We compiled reported HPS cases in northwestern Argentina during the 1997-2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks.
Asunto(s)
Clima , Brotes de Enfermedades/estadística & datos numéricos , Síndrome Pulmonar por Hantavirus/epidemiología , Argentina/epidemiología , Síndrome Pulmonar por Hantavirus/transmisión , Humanos , Lluvia , Virus Sin Nombre , TemperaturaRESUMEN
Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers: NCT04032717, NCT02875119) and has shown broad-spectrum in vivo activity against other viruses, including severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope protein function during entry. 3mGRFT is more potent than GRFT against ANDV and SNV infection. Our results warrant the testing of GRFT and 3mGRFT against ANDV infection in animal models.
Asunto(s)
Antivirales/farmacología , Síndrome Pulmonar por Hantavirus/virología , Lectinas/farmacología , Orthohantavirus/efectos de los fármacos , Virus Sin Nombre/efectos de los fármacos , Técnicas de Cultivo de Célula , Línea Celular , Orthohantavirus/fisiología , Síndrome Pulmonar por Hantavirus/tratamiento farmacológico , Humanos , Virus Sin Nombre/fisiologíaRESUMEN
Sin Nombre virus (SNV) is the major cause of hantavirus cardiopulmonary syndrome (HCPS) in North America, a severe respiratory disease with a high fatality rate. SNV is carried by Peromyscus maniculatus, or deer mice, and human infection occurs following inhalation of aerosolized virus in mouse excreta or secreta, often in peri-domestic settings. Currently there are no FDA approved vaccines or therapeutics for SNV or any other hantaviruses, therefore prevention of infection is an important means of reducing the disease burden of HCPS. One approach for preventing HCPS cases is to prevent the spread of the virus amongst the rodent reservoir population through bait vaccination. However, bait style vaccines for rodent-borne viruses have not been employed in the field, unlike those targeting larger species. Here we utilized a recombinant vesicular stomatitis virus expressing SNV glycoprotein precursor (rVSVΔG/SNVGPC) in an attempt to prevent SNV transmission. Vaccination of deer mice with rVSVΔG/SNVGPC was able to reduce viral RNA copy numbers in the blood and lungs of directly infected animals. More importantly, vaccination, either intramuscularly or orally, significantly reduced the number of transmission events in a SNV transmission model compared with control animals. This provides a proof-of-concept in which oral vaccination of deer mice results in protection against acquiring the virus following direct contact with infected deer mice. Further development of bait style vaccines for SNV or other rodent-borne viruses could provide an effective means of reducing disease burden.
Asunto(s)
Glicoproteínas/inmunología , Síndrome Pulmonar por Hantavirus , Enfermedades de los Roedores , Virus Sin Nombre , Proteínas Virales/inmunología , Vacunas Virales , Animales , Anticuerpos Antivirales , Síndrome Pulmonar por Hantavirus/prevención & control , Síndrome Pulmonar por Hantavirus/veterinaria , Ratones , América del Norte , Peromyscus , Enfermedades de los Roedores/prevención & control , Enfermedades de los Roedores/virología , Vacunación , Virus de la Estomatitis Vesicular IndianaAsunto(s)
Mordeduras y Picaduras/complicaciones , Disnea/etiología , Síndrome Pulmonar por Hantavirus/diagnóstico , Virus Sin Nombre/aislamiento & purificación , Animales , Anticuerpos Antivirales/sangre , Broncoscopía , Tos/etiología , Diagnóstico Diferencial , Fiebre/etiología , Síndrome Pulmonar por Hantavirus/complicaciones , Síndrome Pulmonar por Hantavirus/transmisión , Humanos , Recuento de Leucocitos , Leucocitosis/diagnóstico , Leucocitosis/etiología , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Ratones , Peromyscus , Neumonía/diagnóstico , Virus Sin Nombre/inmunología , Trombocitopenia/diagnóstico , Trombocitopenia/etiología , Tomografía Computarizada por Rayos X , Vapeo/efectos adversos , Adulto JovenRESUMEN
In 2012, a total of 9 cases of hantavirus infection occurred in overnight visitors to Yosemite Valley, Yosemite National Park, California, USA. In the 6 years after the initial outbreak investigation, the California Department of Public Health conducted 11 rodent trapping events in developed areas of Yosemite Valley and 6 in Tuolumne Meadows to monitor the relative abundance of deer mice (Peromyscus maniculatus) and seroprevalence of Sin Nombre orthohantavirus, the causative agent of hantavirus pulmonary syndrome. Deer mouse trap success in Yosemite Valley remained lower than that observed during the 2012 outbreak investigation. Seroprevalence of Sin Nombre orthohantavirus in deer mice during 2013-2018 was also lower than during the outbreak, but the difference was not statistically significant (p = 0.02). The decreased relative abundance of Peromyscus spp. mice in developed areas of Yosemite Valley after the outbreak is probably associated with increased rodent exclusion efforts and decreased peridomestic habitat.
Asunto(s)
Infecciones por Hantavirus/epidemiología , Orthohantavirus/aislamiento & purificación , Animales , California/epidemiología , Reservorios de Enfermedades , Infecciones por Hantavirus/virología , Humanos , Ratones/virología , Parques Recreativos , Virus Sin Nombre/aislamiento & purificaciónRESUMEN
We describe a case of hantavirus pulmonary syndrome in a patient exposed to Sin Nombre virus in a coastal county in California, USA, that had no previous record of human cases. Environmental evaluation coupled with genotypic analysis of virus isolates from the case-patient and locally trapped rodents identified the likely exposure location.
Asunto(s)
Síndrome Pulmonar por Hantavirus/epidemiología , Virus Sin Nombre , Adulto , Animales , California/epidemiología , Vectores de Enfermedades , Humanos , Peromyscus/virología , Filogenia , Roedores/virología , Virus Sin Nombre/genéticaRESUMEN
Andes virus (ANDV) and Sin Nombre virus (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in the Americas. HCPS is a severe respiratory disease with a high fatality rate for which there are no approved therapeutics or vaccines available. Some vaccine approaches for HCPS have been tested in preclinical models, but none have been tested in infectious models in regard to their ability to protect against multiple species of HCPS-causing viruses. Here, we utilize recombinant vesicular stomatitis virus-based (VSV) vaccines for Andes virus (ANDV) and Sin Nombre virus (SNV) and assess their ability to provide cross-protection in infectious challenge models. We show that, while both rVSVΔG/ANDVGPC and rVSVΔG/SNVGPC display attenuated growth as compared to wild type VSV, each vaccine is able to induce a cross-reactive antibody response. Both vaccines protected against both homologous and heterologous challenge with ANDV and SNV and prevented HCPS in a lethal ANDV challenge model. This study provides evidence that the development of a single vaccine against HCPS-causing hantaviruses could provide protection against multiple agents.
Asunto(s)
Anticuerpos Antivirales/sangre , Protección Cruzada , Síndrome Pulmonar por Hantavirus/prevención & control , Orthohantavirus/inmunología , Virus Sin Nombre/inmunología , Vesiculovirus/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Cricetinae , Femenino , Mesocricetus , Vacunación , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Vesiculovirus/genética , Proteínas Virales de Fusión/administración & dosificación , Proteínas Virales de Fusión/inmunología , Vacunas Virales/genéticaRESUMEN
INTRODUCTION: Hantavirus pulmonary syndrome (HPS) is a rare and sometimes fatal respiratory disease in humans. The infection is acquired mainly through inhalation of aerosolized rodent secretions which serves as the reservoir for the virus. HPS cases are mostly reported from the American continent. In this article we describe a case of fulminant HPS in a 47 years old man who had traveled with his family on vacation to the southwestern region of the United States. The patient was hospitalized one month after his return to Israel and the diagnosis of hantavirus infection (species Sin Nombre Virus), was performed on samples sent to the CDC's Viral Special Pathogens Branch. Clinicians should be aware of this special entity and consider HPS in the differential diagnosis of patients with respiratory failure and fever, when there is a history of travel to the endemic area.