Chikungunya Virus Exposure Partially Cross-Protects against Mayaro Virus Infection in Mice.

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest virus antigenic complex classified as belonging to the genus Alphavirus of the family Togaviridae. These viruses cause human disease, with sudden fever and joint inflammation that can persist for long periods. CHIKV is the causative agent of large outbreaks worldwide, and MAYV infection represents a growing public health concern in Latin America, causing sporadic cases and geographically limited outbreaks. Considering the relationship between CHIKV and MAYV, the present study aimed to evaluate if preexisting CHIKV immunity protects against MAYV infection. Immunocompetent C57BL/6 mice were intraperitoneally infected with CHIKV and, 4 weeks later, they were infected with MAYV in their hind paw. We observed that the preexistence of CHIKV immunity conferred partial cross-protection against secondary MAYV infection, reducing disease severity, tissue viral load, and histopathological scores. Interestingly, CHIKV antibodies from humans and mice showed low cross-neutralization to MAYV, but neutralizing activity significantly increased after secondary infection. Furthermore, depletion of adaptive immune cells (CD4+ T, CD8+ T, and CD19+ B cells) did not alter the cross-protection phenotype, suggesting that distinct cell subsets or a combination of adaptive immune cells stimulated by CHIKV are responsible for the partial cross-protection against MAYV. The reduction of proinflammatory cytokines, such as interferon gamma (IFN-γ), in animals secondarily infected by MAYV, suggests a role for innate immunity in cross-protection. Our findings shed light on how preexisting immunity to arthritogenic alphaviruses may affect secondary infection, which may further develop relevant influence in disease outcome and viral transmission. IMPORTANCE Mosquito-borne viruses have a worldwide impact, especially in tropical climates. Chikungunya virus has been present mostly in developing countries, causing millions of infections, while Mayaro virus, a close relative, has been limited to the Caribbean and tropical regions of Latin America. The potential emergence and spread of Mayaro virus to other high-risk areas have increased the scientific community's attention to an imminent worldwide epidemic. Here, we designed an experimental protocol of chikungunya and Mayaro virus mouse infection, which develops a measurable and quantifiable disease that allows us to make inferences about potential immunological effects during secondary virus infection. Our results demonstrate that previous chikungunya virus infection is able to reduce the severity of clinical outcomes during secondary Mayaro infection. We provide scientific understanding of immunological features during secondary infection with the closely related virus, thus assisting in better comprehending viral transmission and the pathological outcome of these diseases.

In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease.

Mayaro virus (MAYV) is endemic in South American countries where it is responsible for sporadic outbreaks of acute febrile illness. The hallmark of MAYV infection is a highly debilitating and chronic arthralgia. Although MAYV emergence is a potential threat, there are no specific therapies or licensed vaccine. In this study, we developed a murine model of MAYV infection that emulates many of the most relevant clinical features of the infection in humans and tested a live-attenuated MAYV vaccine candidate (MAYV/IRES). Intraplantar inoculation of a WT strain of MAYV into immunocompetent mice induced persistent hypernociception, transient viral replication in target organs, systemic production of inflammatory cytokines, chemokines and specific humoral IgM and IgG responses. Inoculation of MAYV/IRES in BALB/c mice induced strong specific cellular and humoral responses. Moreover, MAYV/IRES vaccination of immunocompetent and interferon receptor-defective mice resulted in protection from disease induced by the virulent wt MAYV strain. Thus, this study describes a novel model of MAYV infection in immunocompetent mice and highlights the potential role of a live-attenuated MAYV vaccine candidate in host's protection from disease induced by a virulent MAYV strain.

Momento de considerar otras arbovirosis luego del virus mayaro / Time to Consider Other Arbovirus Diseases after mayaro Virus

Introducción: En los últimos años, debido a los movimientos migratorios, se ha desarrollado una expansión de nuevas enfermedades, como chikungunya, zika, oropuche y mayaro. Caso clínico: Paciente que manifestaba síntomas de fiebre, cefalea y artralgias persistente. Después de un arduo estudio y eliminación de otras patologías se llega al diagnóstico de virus mayaro. El paciente residía en una zona nororiental del Perú. Se brindó tratamiento de soporte junto con hidratación, paracetamol 500 mg cada 8 horas y se indicó cita diaria para evaluación. El paciente evolucionó favorablemente a los pocos días. Conclusiones: La vigilancia, las pruebas y el control vectorial siguen siendo claves para prevenir la propagación de este tipo de virus. La posibilidad de que el virus mayaro se urbanice aún más. Se debe tener siempre en cuenta el diagnóstico diferencial de virus mayaro(AU)

Introduction: In recent years, due to migratory movements, an expansion of new diseases has developed, such as chikungunya, zika, oropuche and mayaro. Clinical case: Patient with the following symptoms: fever, headache and persistent arthralgia. After an arduous study and ruling out other possible diseases, we diagnose mayaro virus. The patient resided in a northeastern part of Peru. Supportive treatment was provided along with hydration; paracetamol 500 mg every 8 hours and daily appointment for evaluation was indicated. The patient evolved favorably within a few days. Conclusions: Surveillance, testing and vector control are still key to monitoring and preventing the spread of this type of virus. The possibility of mayaro virus becoming more urbanized is worthy of attention. The differential diagnosis of mayaro virus should always be considered(AU)

Venezuelan and western equine encephalitis virus E1 liposome antigen nucleic acid complexes protect mice from lethal challenge with multiple alphaviruses.

Eastern, Venezuelan and western equine encephalitis viruses (EEEV, VEEV, and WEEV) are mosquito-borne viruses that cause substantial disease in humans and other vertebrates. Vaccines are limited and current treatment options have not proven successful. In this report, we vaccinated outbred mice with lipid-antigen-nucleic acid-complexes (LANACs) containing VEEV E1+WEEV E1 antigen and characterized protective efficacy against lethal EEEV, VEEV, and WEEV challenge. Vaccination resulted in complete protection against EEEV, VEEV, and WEEV in CD-1 mice. Measurements of bioluminescence and plaque reduction neutralization tests (PRNTs) indicate that LANAC VEEV E1+WEEV E1 vaccination is sterilizing against VEEV and WEEV challenge; whereas immunity to EEEV is not sterilizing. Passive transfer of rabbit VEEV E1+WEEV E1 immune serum to naive mice extended the mean time to death (MTD) of EEEV challenged mice and provided significant protection from lethal VEEV and WEEV challenge.

Fiebre causada por el virus Chikungunya, enfermedad emergente que demanda prevención y control / Fever caused by Chikungunya virus, an emergent disease demanding prevention and control

En la región de las Américas, la fiebre causada por el virus chikungunya, ha sido notificada recientemente. Al ser una enfermedad emergente y ante la presencia del mosquito transmisor, el Aedes aegypti, en Cuba y casi toda el área geográfica, resulta necesario su prevención y control, para evitar que se registren brotes de la misma. Se realizó una revisión bibliográfica de los principales artículos publicados sobre el tema, resumiendo los aspectos fundamentales de este problema de salud(AU)

In the region of the Americas, the fever caused by the Chikungunya virus has been notified recently. Being an emergent disease, and because of the presence of the transmitting mosquito, the Aedes aegypti, in Cuba and at around almost all the geographic area, it is necessary its prevention and control, to avoid disease outbreaks. We carried out a bibliographic review of the main articles published on the theme, reviewing the main aspects of this health problem(AU)

Fiebre de Chikungunya: enfermedad infrecuente como emergencia médica en Cuba / Chikungunya fever: uncommon disease as a medical emergency in Cuba

Debido a la emergencia en el Caribe por fiebre de Chikungunya, y teniendo en cuenta que no tiene antecedentes en Cuba, además de la situación entomológica que presenta la provincia de Santiago de Cuba, donde existen vectores transmisores de enfermedades, tales como mosquitos Aedes aegypti y Aedes albopictus; se realizó una revisión bibliográfica exhaustiva, para contribuir a la actualización sobre el tema de toda la comunidad médica de la provincia.

Due to the emergency in the Caribbean caused by Chikungunya fever, and keeping in mind that it has no history in Cuba, besides the entomological situation that presents Santiago de Cuba province, where vectors transmitting diseases exist, such as Aedes aegypti and Aedes albopictus mosquitoes, an exhaustive literature review was carried out, to contribute to the updating on the topic of the whole medical community from the province.

Novel vaccination approaches against equine alphavirus encephalitides.

The current production of inactivated vaccines for the prevention of equine alphavirus encephalitides caused by Eastern, Western and Venezuelan Equine Encephalitis viruses (EEEV, WEEV, VEEV) involves the manipulation of large quantities of infectious viral particles under biosafety level 3 containment laboratories with the potential risk of transmission to the operators. Moreover, these vaccines are not capable of inducing a long-lasting immunity. Modified live vaccines, which were also attempted, maintain residual virulence and neurotropism, causing disease in both horses and humans. Therefore, the production of an efficacious second generation vaccine which could be used in the prevention of alphavirus infection without the need to manipulate infectious viral particles under high biocontainment conditions could be of great benefit for the worldwide horse industry. Furthermore, equine alphaviruses are considered as biological threat agents. Subunit, chimeric, gene-deleted live mutants, DNA and adenovirus-vectored alphavirus vaccines have been evaluated; such approaches are reviewed in this work. Climate changes, together with modifications in bird and vector ecology, are leading to the arise of emerging pathogens in new geographical locations, and these zoonotic New World arboviruses are gaining concern. Novel vaccine development does show a promising future for prevention of these infections in both horses and humans.

Preparação e resposta à introdução do vírus Chikungunya no Brasil / Preparation and response to introduction of Chikungunya virus in Brazil / Preparación y respuesta a la introducción del virus Chikungunya en Brasil

O CHIKV é um vírus RNA que pertence ao gênero Alphavírus da família Togaviridae. O nome chikungunya deriva de uma palavra em Makonde que significa aproximadamente “aqueles que se dobram”, descrevendo a aparência encurvada de pacientes que sofrem de artralgia intensa. Casos humanos com febre, exantema e artrite aparentando ser CHIKV foram relatados no início de 1770. Porém, o vírus não foi isolado do soro humano ou de mosquitos até a epidemia na Tanzânia de 1952-53. Outros surtos ocorreram subsequentemente na África e na Ásia. Muitos ocorreram em pequenas comunidades ou comunidades rurais. No entanto,na Ásia, cepas de CHIKV foram isoladas durante grandes surtos urbanos em Bangkok eTailândia em 1960 e em Calcutá e Vellore, na Índia, durante as décadas de 60 e 70.

[From donor to recipient: transfusion chain specificities in the French ultra-marine areas]. / Du donneur au receveur: particularités de la chaîne transfusionnelle dans les DOM.

Besides specific organisational requirements, the transfusional chain in French ultra-marine areas has specificities related to the epidemiology of infectious diseases and to population characteristics. We focus on some of these sociodemographic and medical peculiarities: the challenge of autosufficiency in relation to demographic trends; epidemiologic risks associated to emergent viruses such as dengue and Chikungunya, and the strategies that had been implemented to face last outbreaks; inappropriate selection criteria for eligibility to blood donation (biologic characteristics of Afro-Caribbeans not taken into account for the low hemoglobin deferral threshold; absence of guidelines for the screening of hemoglobinopathies AS/AC, present in 8% of the target population); specific indications for transfusion, such as platelet use in dengue fever or RBC transfusion in sickle cell disease. Due to the high polymorphism of erythrocyte antigens in Afro-Caribbeans, intra-ethnic transfusion facilitates compatibility for common antigens, but is responsible for the emergence of allo-antibodies difficult to identify in the absence of specific antisera or panels; molecular typing of erythrocyte antigens would allow detection of those patients at risk for immunization, expressing variant antigens or lacking high frequency antigens, as well as the characterization of RBC expressing immunogenic so called low frequency antigens. In an era of periodic emergence of new viruses in Europe (dengue, Chikungunya, West Nile virus...) and with the spreading of diseases with high transfusional requirements, such as sickle cell disease, ultra-marine services represent laboratories for the study of future trends and problems in transfusion medicine.

Why do we need alternative tools to control mosquito-borne diseases in Latin America?

In this opinion paper, we discuss the potential and challenges of using the symbiont Wolbachia to block mosquito transmitted diseases such as dengue, malaria and chikungunya in Latin America.

Why do we need alternative tools to control mosquito-borne diseases in Latin America?

In this opinion paper, we discuss the potential and challenges of using the symbiont Wolbachia to block mosquito transmitted diseases such as dengue, malaria and chikungunya in Latin America.

A humanised murine monoclonal antibody protects mice from Venezuelan equine encephalitis virus, Everglades virus and Mucambo virus when administered up to 48 h after airborne challenge.

Currently there are no licensed antiviral treatments for the Alphaviruses Venezuelan equine encephalitis virus (VEEV), Everglades virus and Mucambo virus. We previously developed a humanised version of the mouse monoclonal antibody 1A3B-7 (Hu1A3B-7) which exhibited a wide range of reactivity in vitro and was able to protect mice from infection with VEEV. Continued work with the humanised antibody has now demonstrated that it has the potential to be a new human therapeutic. Hu1A3B-7 successfully protected mice from infection with multiple Alphaviruses. The effectiveness of the humanisation process was determined by assessing proliferation responses in human T-cells to peptides derived from the murine and humanised versions of the V(H) and V(L) domains. This analysis showed that the number of human T-cell epitopes within the humanised antibody had been substantially reduced, indicating that Hu1A3B-7 may have reduced immunogenicity in vivo.

Chikungunya virus infection: report of the first case diagnosed in Rio de Janeiro, Brazil / Infecção pelo virus Chikungunya: relato do primeiro caso diagnosticado no Rio de Janeiro, Brasil

Initially diagnosed in Africa and Asia, the Chikungunya virus has been detected in the last three years in the Caribbean, Italy, France, and the United States of America. Herein, we report the first case for Rio de Janeiro, Brazil, in 2010.

Antes diagnosticado na África e na Ásia, o vírus Chikungunya foi detectado nos últimos três anos, no Caribe, na Itália, na França e nos Estados Unidos. Relatamos o primeiro caso do Rio de Janeiro, Brasil, em 2010.

Preparación y respuesta ante la eventual introducción del virus chikungunya en las Américas / Preparation and response to the eventual introduction of the virus Chikungunya in the Americas

Las siguientes guías fueron concebidas para ser adaptadas por cada País Miembro para mejorar los conocimientos sobre esta amenaza y para brindar las herramientas necesarias que permitan establecer las estrategias más adecuada para prevenir la importación de CHIKV a la Región, o para su control. Proporcionan orientación sobre cómo detectar un brote de la enfermedad, desarrollar las investigaciones epidemiológicas y prevenir o mitigar la diseminación de la enfermedad en la Región. Alentamos a las personas involucradas en la aplicación de estas guías a tener en cuenta todos los conocimientos disponibles y la capacidad propia de cada país para afrontar la eventual introducción del CHIKV. Se deben tomar medidas cuanto antes para poner en marcha las acciones necesarias para disminuir el impacto que este nuevo arbovirus que puede existir en nuestra Región.

Vaccination with recombinant Semliki Forest virus particles expressing translation initiation factor 3 of Brucella abortus induces protective immunity in BALB/c mice.

Recombinant replicons of Semliki Forest virus (SFV) can be used to induce high-level, transient expression of heterologous proteins in vivo. We constructed infectious but replication-deficient SFV particles carrying recombinant RNA encoding the Brucella abortus translation initiation factor 3 (IF3). The recombinant SFV particles (SFV-IF3 particles) were then evaluated for their ability to induce immune responses and to protect BALB/c mice against a challenge with B. abortus 2308 following vaccination. Animals inoculated with SFV-IF3 developed IF3-specific IgM antibodies at day 14 post-immunization. In vitro stimulation of splenocytes from vaccinated mice with either recombinant IF3 (rIF3) or crude Brucella protein extracts resulted in a T-cell proliferative response and induction of interferon gamma secretion, but not interleukin-4. In addition, mice immunized with SFV-IF3 exhibited a significant level of resistance against challenge with the virulent B. abortus strain 2308 (P<0.01). These findings indicate that an SFV-based vector carrying RNA encoding Brucella IF3 has potential for use as a vaccine to induce protection against B. abortus infections.