RESUMEN
Equine herpesvirus 1 (EHV-1) causes respiratory disease, abortion, neonatal death and neurological disease in equines and is endemic in most countries. The viral factors that influence EHV-1 disease severity are poorly understood, and this has hampered vaccine development. However, the N752D substitution in the viral DNA polymerase catalytic subunit has been shown statistically to be associated with neurological disease. This has given rise to the term "neuropathic strain," even though strains lacking the polymorphism have been recovered from cases of neurological disease. To broaden understanding of EHV-1 diversity in the field, 78 EHV-1 strains isolated over a period of 35 years were sequenced. The great majority of isolates originated from the United Kingdom and included in the collection were low passage isolates from respiratory, abortigenic and neurological outbreaks. Phylogenetic analysis of regions spanning 80% of the genome showed that up to 13 viral clades have been circulating in the United Kingdom and that most of these are continuing to circulate. Abortion isolates grouped into nine clades, and neurological isolates grouped into five. Most neurological isolates had the N752D substitution, whereas most abortion isolates did not, although three of the neurological isolates from linked outbreaks had a different polymorphism. Finally, bioinformatic analysis suggested that recombination has occurred between EHV-1 clades, between EHV-1 and equine herpesvirus 4, and between EHV-1 and equine herpesvirus 8.
Asunto(s)
Aborto Veterinario/virología , Encefalopatías/veterinaria , Variación Genética , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/genética , Enfermedades de los Caballos/virología , Trastornos Respiratorios/veterinaria , Animales , Secuencia de Bases , Encefalopatías/virología , ADN Viral/genética , ADN Polimerasa Dirigida por ADN/genética , Brotes de Enfermedades/veterinaria , Equidae , Femenino , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Herpesvirus Équido 1/aislamiento & purificación , Enfermedades de los Caballos/epidemiología , Caballos , Filogenia , Embarazo , Trastornos Respiratorios/virología , Reino UnidoRESUMEN
Equine influenza virus is a major respiratory pathogen in horses, and outbreaks of disease often lead to substantial disruption to and economic losses for equestrian industries. The hemagglutinin (HA) protein is of key importance in the control of equine influenza because HA is the primary target of the protective immune response and the main component of currently licensed influenza vaccines. However, the influenza virus HA protein changes over time, a process called antigenic drift, and vaccine strains must be updated to remain effective. Antigenic drift is assessed primarily by the hemagglutination inhibition (HI) assay. We have generated HI assay data for equine influenza A (H3N8) viruses isolated between 1968 and 2007 and have used antigenic cartography to quantify antigenic differences among the isolates. The antigenic evolution of equine influenza viruses during this period was clustered: from 1968 to 1988, all isolates formed a single antigenic cluster, which then split into two cocirculating clusters in 1989, and then a third cocirculating cluster appeared in 2003. Viruses from all three clusters were isolated in 2007. In one of the three clusters, we show evidence of antigenic drift away from the vaccine strain over time. We determined that a single amino acid substitution was likely responsible for the antigenic differences among clusters.
Asunto(s)
Evolución Molecular , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H3N8 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/virología , Sustitución de Aminoácidos , Animales , Antígenos Virales/clasificación , Antígenos Virales/inmunología , Western Blotting , Células Cultivadas , Perros , Pruebas de Inhibición de Hemaglutinación , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Hemaglutininas/inmunología , Hemaglutininas/metabolismo , Caballos , Subtipo H3N8 del Virus de la Influenza A/aislamiento & purificación , Riñón/citología , Riñón/metabolismo , Riñón/virología , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/inmunología , Filogenia , ARN Mensajero/genética , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoRESUMEN
Recently, glycoprotein G (gG) of several alphaherpesviruses infecting large herbivores was shown to belong to a new family of chemokine-binding proteins (vCKBPs). In the present study, the function of Felid herpesvirus 1 (FeHV-1) gG as a vCKBP was investigated and the following conclusions were reached: (i) FeHV-1 secreted gG is a high-affinity broad-spectrum vCKBP that binds CC, CXC and C chemokines; (ii) gG is the only vCKBP expressed by FeHV-1 that binds CCL3 and CXCL1; (iii) secreted gG blocks chemokine activity by preventing their interaction with high-affinity cellular receptors; (iv) the membrane-anchored form of gG expressed on the surface of infected cells is also able to bind chemokines; and (v) the vCKBP activity is conserved among different field isolates of FeHV-1. Altogether, these data demonstrate that FeHV-1 gG is a new member of the vCKBP-4 family. Moreover, this study is the first to demonstrate that gG expressed at the surface of FeHV-1-infected cells can also bind chemokines.
Asunto(s)
Quimiocinas/metabolismo , Varicellovirus/fisiología , Proteínas del Envoltorio Viral/metabolismo , Quimiocinas/antagonistas & inhibidores , Quimiocinas C/metabolismo , Quimiocinas CC/metabolismo , Quimiocinas CXC/metabolismo , ADN Viral/química , Datos de Secuencia Molecular , Unión Proteica , Análisis de Secuencia de ADNRESUMEN
Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-gamma (IFN-gamma). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-kappaB activation and induction of IFN-gamma in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.
Asunto(s)
Glicoproteínas/genética , Glicoproteínas/metabolismo , Orthopoxvirus/genética , Orthopoxvirus/metabolismo , Secuencia de Aminoácidos , Animales , Baculoviridae/genética , Línea Celular , Virus de la Viruela Vacuna/genética , Virus de la Viruela Vacuna/metabolismo , Medios de Cultivo , Virus de la Ectromelia/genética , Virus de la Ectromelia/metabolismo , Glicoproteínas/química , Humanos , Péptidos y Proteínas de Señalización Intercelular , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Virus del Molusco Contagioso/genética , Virus del Molusco Contagioso/metabolismo , Proteínas Recombinantes/metabolismo , Bazo/citología , Bazo/metabolismo , Virus Vaccinia/genética , Virus Vaccinia/metabolismoAsunto(s)
Servicios de Salud del Niño/legislación & jurisprudencia , Personas con Discapacidad/legislación & jurisprudencia , Ética , Política de Salud , Accesibilidad a los Servicios de Salud/legislación & jurisprudencia , Niño , Personas con Discapacidad/educación , Personas con Discapacidad/rehabilitación , Educación Especial/economía , Educación Especial/legislación & jurisprudencia , Reforma de la Atención de Salud/historia , Reforma de la Atención de Salud/legislación & jurisprudencia , Accesibilidad a los Servicios de Salud/economía , Historia del Siglo XX , Humanos , Calidad de la Atención de Salud/economía , Calidad de la Atención de Salud/legislación & jurisprudencia , Estados UnidosRESUMEN
Recent proposals to reform Medicaid, driven primarily by the need for cost containment, rarely pay explicit attention to values. This paper presents the Medicaid Values Framework, the authors' interpretation of a set of societal ideals embodied in Title XIX of the Social Security Amendments of 1965. The Framework comprises seven interlocking values that are stratified into three interdependent tiers--access, quality, and equity. We use the access and equity tiers to analyze treatment of Aid to Families with Dependent Children (AFDC) and Supplemental Security Income (SSI) recipients under Medicaid. We document striking inequities in eligibility standards and in funding for the two groups--inequities that unexpectedly fail to translate into marked disparities in access to Medicaid. In conclusion, we comment on why the present inequities exist and why they are ethically unacceptable.