La viruela símica como enfermedad zoonótica viral y reemergente en el actual contexto sanitario mundial / Mpox as a Viral Zoonotic Disease Reemerging in the Current Global Health Context

Introducción: La viruela símica es una enfermedad zoonótica que también se trasmite de persona a persona por contacto estrecho. En el brote actual hasta el 31 de agosto de 2022 se reportaban 50 496 casos diagnosticados en 101 países, por lo que se consideró una situación preocupante por la Organización Mundial de la Salud. Objetivo: Exponer información actualizada sobre la viruela símica en el contexto sanitario actual. Métodos: Se realizó una búsqueda de literatura científica en las bases de datos ScienceDirect, PubMed/Medline, SciELO y Google Académico, mediante los descriptores o palabras relacionadas con la enfermedad, para encontrar revisiones, comunicados, informes, distintos artículos de revistas, entre otros documentos especializados de producción científica. Se seleccionó un total de 30 citas, actualizadas en su totalidad. Desarrollo: Desde su identificación en humanos se han reportado brotes de viruela símica en varios países; el más preocupante, ha sido el de reciente declaración en 2022, debido a la presencia de casos en países no endémicos, con un alcance geográfico extenso. Las manifestaciones clínicas pueden cursar con síntomas leves, como erupciones en la cara y el resto del cuerpo, fiebre, cefalea, mialgias y fatiga, por lo que no constituye una enfermedad potencialmente mortal; sin embargo, de presentarse comorbilidades la evolución podría ser tórpida. Conclusiones: La presencia de casos de viruela símica en humanos se ha mantenido desde su aparición, sin encontrar un tratamiento específico y vacunas autorizadas para su administración, lo que podría generar un aumento de contagios y fallecidos(AU)

Introduction: Mpox is a zoonotic disease also transmitted from person to person by close contact. The current outbreak, up to August 31, 2022, reported 50 496 diagnosed cases from 101 countries; therefore; it was considered a situation of concern by the World Health Organization. Objective: To present updated information on Mpox in the current health context. Methods: A scientific literature search was carried out in the databases ScienceDirect, PubMed/Medline, SciELO and Google Scholar, using descriptors or words related to the disease, in order to find reviews, communications, reports, different journal articles, among other specialized documents of scientific production. A total of 30 entirely updated citations were selected. Development: Since Mpox was identified in humans, outbreaks of the disease have been reported in several countries; the most worrisome has been reported recently in 2022, due to the presence of cases in nonendemic countries, with an extensive geographical scope. The clinical manifestations may occur with mild symptoms, such as rash on the face or the rest of the body, fever, headache, myalgia and fatigue; therefore, it is not a potentially mortal disease. However, in case of comorbidity, the evolution could be torpid. Conclusions: Mpox cases in humans has been present since its appearance, without any specific treatment or vaccines authorized to be administered, which could generate an increase in contagions and deaths(AU)

Diferencias entre formas de contagio intra y extradomiciliaria en tres brotes epidémicos de COVID-19 en Santiago de Cuba / Differences between Forms of Intra- and Extra-Domiciliary Contagion in Three Epidemic Outbreaks of COVID-19 in Santiago de Cuba

Introducción: En la transmisión de la COVID-19 en Santiago de Cuba se distinguieron tres brotes epidémicos entre 2020 y 2021. Objetivo: Identificar las diferencias entre los contagios intra y extradomiciliarios en tres brotes epidémicos de COVID-19 en Santiago de Cuba entre marzo de 2020 y mayo de 2021. Métodos: Se realizó un estudio descriptivo transversal de los casos de COVID-19 del territorio y el período referidos, mediante las técnicas bivariadas habituales de la estadística y el análisis estadístico implicativo, con una muestra de 6408 que se eligió por muestreo aleatorio simple de la base de datos de casos confirmados. Resultados: El contagio extradomiciliario fue significativamente mayor que el intradomiciliario sin diferencias por sexo, pero sí según grupos de edades y municipios dentro y entre ambos grupos. Fue significativo el predominio de los adultos mayores en el contagio intradomiciliario y de los adultos jóvenes en el extradomiciliario. Primaron los sintomáticos en el intradomiciliario; y, los asintomáticos, en el extradomiciliario, sin diferencias significativas entre ambas formas. Los menores de 20 años de edad, adultos mayores, asintomáticos y el municipio Mella fueron las características que se asociaron con el contagio intradomiciliario, mientras, con el extradomiciliario, los adultos jóvenes sintomáticos. Conclusiones: Las formas de contagio intra y extradomiciliaria se modularon según la conducta de las personas y el aislamiento propio de cada grupo de edades. La extradomiciliaria predominó en edades intermedias de la vida, como expresión de la conducta mediada por su responsabilidad económica en el hogar, mientras las edades extremas, que permanecieron en casa por cumplir medidas de aislamiento, fueron más propensas a la intradomiciliaria(AU)

Introduction: In the transmission of COVID-19 in Santiago de Cuba province, three epidemic outbreaks were observed between 2020 and 2021. Objective: To identify the differences between intra- and extra-domiciliary infections in three epidemic outbreaks of COVID-19 in Santiago de Cuba between March 2020 and May 2021. Methods: A cross-sectional descriptive study of COVID-19 cases in the territory and period above mentioned was carried out, using the usual bivariate techniques of statistics and implicative statistical analysis, to a sample of 6408 cass that was chosen by simple random sampling from the database of confirmed cases. Results: Extra-domiciliary contagion was significantly higher than intra-domiciliary contagion without differences by sex, but according to age groups and municipalities within and between both groups. The predominance of older adults in intra-domiciliary contagion and of young adults in extra-domiciliary contagion was significant. Symptomatic patients prevailed in the intra-domiciliary; and, the asymptomatic, in the extra-domiciliary, without significant differences between both forms. Children under 20 years of age, older adults, asymptomatic and Mella municipality were the characteristics that were associated with intra-domiciliary contagion, while, with the extra-domiciliary were related symptomatic young adults. Conclusions: The forms of intra- and extra-domiciliary contagion were modulated according to the behavior of the people and the isolation of each age group. Extra-domiciliary predominated in intermediate ages of life, as an expression of the behavior mediated by their economic responsibility at home, while extreme ages, who remained at home to comply with isolation measures, were more prone to intra-domiciliary contagion(AU)

Brote de Parotiditis Vírica en el Liceo Militar de Acosta Ñu de junio a octubre del año 2016 / Outbreak of Viral Parotitis at the Acosta Ñu Military Academy from june to october 2016

Introducción: El presente estudio trata de un brote de parotiditis en un Liceo Militar que se inicia en junio del año 2016 y se prolonga hasta fines de octubre del mismo año. El objetivo fue describir las características epidemiológicas del brote. Métodos: Es observacional, retroprospectivo, de corte transverso de fichas clínicas de cadetes que constan en el archivo del Liceo Militar de Acosta Ñu que abarca el periodo junio a octubre del año 2016 y posterior entrevista a los afectados. Resultados: De 181 cadetes, todos masculinos, con edad media de 16 años, del Liceo Militar de Acosta Ñu. Se tomó como muestra a 115 cadetes (63%) presentaron parotiditis, sin afectación de las otras glándulas salivales. En 50 casos (44%) de forma bilateral y 64 casos (56%) unilateral. 23 cadetes (20%) presentaron complicaciones, como orquitis 22 (19%) todos unilaterales, pancreatitis 1. En ningún caso se presentó meningitis, encefalitis, miocarditis, todos sobrevivieron. De los cadetes afectados no fueron vacunados (SPR) 103 (90%), 8 (7%) recibieron una dosis y 2 (2.3%) dos dosis. Los casos ocurridos (63%) fue debida a la falta de vacunación completa (Triple Viral, 2 dosis) y a las condiciones de hacinamiento de los cadetes. Conclusión: El brote de parotiditis ocurrido en el Liceo Militar de Acosta Ñu, se caracterizó por la alta incidencia de contagios debido a la baja o nula cobertura vacunal y a las condiciones de hacinamiento de los cadetes. Por lo tanto recomendamos que al ingreso a toda institución que incluya residencia temporal o fija en condiciones de hacinamiento, la exigencia mínima debiera ser la presentación de un carnet de vacunación completo.

Introduction: This study describes an outbreak of mumps in a Military Academy that began in June 2016 and lasted until the end of October of the same year. Objective: To describe the epidemiological characteristics of the outbreak. Materials and Methods: This was an observational, retroprospective, cross-sectional review of the medical records of cadets at the Acosta Ñu Military Academy who presented for medical evaluation from June to October, 2016 and with subsequent interviews with identified patients with parotitis. Results: Of 181 cadets, all were male, with an average age of 16 years. We selected a sample of 115 cadets (63%) who presented parotiditis, without involvement of other salivary glands. In 50 cases (44%) the illness was bilateral and in 64 cases (56%), the illness was unilateral. 23 cadets (20%) presented complications, such as orchitis 22 (19%) all unilateral, and one patient had pancreatitis. No patient had meningitis, encephalitis, or myocarditis, and there were no deaths. Of the affected 103 (90%) cadets were not vaccinated with the measles-mumps-rubella (MMR) vaccine, 8 (7%) had received one dose and 2 (2.3%) received two doses. The cases that occurred (63%) were due to the lack of complete vaccination (MMR vaccine, 2 doses) and to the overcrowded conditions of the cadets. Conclusion: The Outbreak of parotitis, which occurred at Acosta Ñu Military Academy, was characterized by a high incidence of infections due to incomplete or no vaccination coverage and the overcrowded conditions of the cadets. Therefore, we recommend that upon admission to any institution that includes temporary or fixed residence in overcrowded conditions, the minimum requirement should be the presentation of a completed vaccination card.

ÁNTRAX: enfermedad aún vigente / ANTHRAX: disease still current

El ántrax es una zoonosis producida por Bacillus anthracis, único miembro del género Bacillus que es capaz de causar enfermedad epidémica en humanos y otros mamíferos. Afecta principalmente a los animales herbívoros domésticos y silvestres. Los humanos son hospederos accidentales y se infectan por contacto directo o indirecto con animales o productos contaminados. Las esporas pueden vivir en el suelo por años y los humanos pueden contraer el ántrax al tener contacto con animales infectados, productos provenientes de estos que al consumir carne infectada; esto se presenta principalmente en países poco desarrollados donde los niveles de vacunación animal contra esta enfermedad son bajos. Este escrito tiene por objetivo presentar una revisión sobre el tema, especialmente sobre aspectos como el modo de infección, manifestaciones clínicas, diagnóstico y tratamiento de la enfermedad.

Anthrax is a zoonosis produced by Bacillus anthracis, the only member of the genus Bacillus that is capable of causing epidemic disease in humans and other mammals. It mainly affects wild and domestic animals. Humans are accidental hosts and are infected through direct or indirect contact with animals or contaminated animal products. B. anthracisspores can live in the soil for many years and humans can become infected with anthraxby contact with infected animals or products contaminated from eating meat infected. This disease occurs mainly in developing countries where vaccine levels are low.The objective of this paper is to present a review on thesubject, especially on aspects such as mode ofinfection, clinical features diagnostic assessment and treatment of thedisease.

Factores relacionados con el control exitoso de un brote por Klebsiella pneumoniae productora de KPC-2 en una unidad de cuidado intensivo en Bogotá, Colombia / Factors related to successful control of an outbreak by Klebsiella pneumonia -producing KPC-2 in an intensive care unit in Bogotá, Colombia

La resistencia a carbapenémicos en Klebsiella pneumoniae ha aumentado de manera considerable, incrementando las tasas de morbimortalidad. El objetivo de este trabajo fue describir las características epidemiológicas, microbiológicas y las medidas de intervención que permitieron el control exitoso de un brote de Klebsiella pneumoniae productora de KPC-2. Métodos: El estudio se realizó en 2 periodos: el primero durante el brote, con instauración de un protocolo de medidas de intervención; y el segundo, de seguimiento posbrote. Se realizaron pruebas de identificación y susceptibilidad por sistema automatizado, tamización de carbapenemasas por test de Hodge modificado, PCR para detección de los genes bla KPC, bla KPC-2, NDM-1 y estudio de clonalidad por electroforesis de campos pulsados. Resultados: Durante el brote, se identificaron 18 aislamientos de Klebsiella pneumoniae productora de KPC en 11 pacientes. Tres casos fueron confirmados como infección intrahospitalaria. La técnica de PCR reveló la presencia del gen bla KPC en 21 de 22 aislamientos (pacientes y medio ambiente) y se identificó la presencia de un clon con una similitud superior al 75%. En el periodo posbrote los cultivos ambientales y de búsqueda de colonizados fueron negativos. Discusión: Se evidenció un control exitoso del brote producido por un clon. La implementación de un protocolo de intervención y la monitorización de su cumplimiento, la comunicación efectiva y el trabajo en equipo fueron indispensables para evitar su propagación y evitar un comportamiento endémico posbrote.

The considerable increase in carbapenem-resistant Klebsiella pneumoniae has caused an increase in mortality and morbidity rates. The aim of this study was to describe its epidemiological and microbiological characteristics and the intervention measures that controlled an outbreak caused by K. pneumoniae- producing KPC-2 B-lactamase. Methods: The study was divided into 2 periods: the first during the outbreak with the implementation of a bundle and the second a post-outbreak surveillance. We performed tests for identification and susceptibility by using an automated system, screening carbapenemases by the Modified-Hodge test, bla KPC, bla KPC-2 and NDM-1 identification by PCR and clonal relationship characterisation by PFGE. Results: During the outbreak, there were 18 isolates of Klebsiella pneumoniae -producing KPC- 2 in 11 patients. Three cases were confirmed as hospital-acquired infection. Of 22 isolates, 21 were positive to bla KPC by PCR (samples from patients and environment) and a clone was identified with a similarity of greater than 75%. During the post-outbreak surveillance, we did not find any new positive cultures from surfaces and there were no new colonisations. Discussion: This was a successful control of an outbreak produced by a clone. The implementation of a bundle and a subsequent surveillance to monitor its fulfilment, effective communication and teamwork were crucial to inhibit propagation of the infection and to prevent an endemic behaviour post-outbreak.

Inhibition of HBV Release by BST-2 / 病毒学报

Bone marrow stromal antigen 2 (BST-2) is a kind of host restriction factor. Since it was discovered to be responsible for the defect in virion release of HIV-1 mutants lacking the accessory gene vpu in 2008, it was thought to mainly restrict the viruses by directly tethering viral particles at the plasma membrane. Recent reports suggest that BST-2 also can inhibit the the release of HBV particles, which are budding in the intracellular vesicles, expanding the antiviral spectrum of BST-2. Futhermore, the machanism that BST-2 used to restrict HBV release in multivesicular bodies (MVBs) is similar to that used to restrict HIV at the plasma membrane. However, HBV have evolved strategies to antagonize the antiviral action of BST-2. There are two different opinions about the antagonist. One is HBV inactivated BST-2 by HBx requiring a hepatocyte-specific environment. Another thought envelope protein HBs counteract the antiviral action of BST-2. In this review, we focus on the current advances in the anti-HBV activity of BST-2.

Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

Morphogenetic study of human adenovirus type 41 in 293TE cells / 病毒学报

To investigate the morphogenetic process of human adenovirus type 41 (HAdV-41), 293TE cells were infected with purified wild-type HAdV-41, and ultrathin sections of infected cells were prepared and observed under a transmission electron microscope. Results showed that HAdV-41 entered host cells mainly through three ways: non-clathrin-coated pit, clathrin-coated pit, and direct penetration of plasma membrane. In addition, cell microvilli might help HAdV-41 enter cells. After entering into cells, HAdV-41 virus particles could be found in vacuoles or lysosomes or be in a free state in cytoplasm. Only free virus particles could be found near nuclear pores (NP), suggesting that the virus needed to escape from lysosomes for effective infection and viral nucleoprotein entered the nucleus through NP. Progeny viruses were as-sembled in the nucleus. Three types of inclusion bodies, which were termed as fibrillous inclusion body, condense inclusion body, and stripped condense inclusion body, were involved in HAdV-41 morphogenesis. In the late phase of viral replication, the membrane integrity of the infected cells was lost and viral particles were released extracellularly. This study reveals the partial process of HAdV-41 morphogenesis and provides more biological information on HAdV-41.

Effects of mutations in the autographa californica multiple nucleopolyhedrovirus E25 on its trafficking to nucleus and budded virus production / 病毒学报

This study was performed to investigate the effects of different regions of the Autographa califor nica multiple nucleopolyhedrovirus envelope protein E25 on its trafficking into nucleus and nuclear localization in host cells and on virus replication. Fourteen recombinant bacmids, each containing an e25 mutant with substitution or insertion of egfp, in the absence or presence of the native e25, were constructed and used to transfect Sf9 cells. The E25-EGFP fusion proteins and native E25 expressed in the cells transfect ed with individual recombinant bacmid were traced by autofluorescence from EGFP or by immuno-fluorescence assays. Confocal microscopy revealed that the E25-EGFP fusion protein with the N-domain (2-45aa) of E25 substituted by EGFP only distributed in the cytoplasm in transfected cells; and the fusion protein with EGFP inserted at the laa/2aa site of E25 completely remained outside of the nucleus and resided along the nuclear membrane. The E25-EGFPs with 46-118aa of E25 substituted by EGFP or with EGFP inserted at the 118aa/119aa site were present outside, across from the nuclear membrane or in nuclear plasm in dot-like shapes. The fusion proteins with the C-domain substituted by EGFP or with EGFP inserted at the site of 45/46aa or at the C-terminal formed a condensed ring or spread throughout the nucleus, in a similar manner to the E25 distributed in the cells transfected by the e25-knockout repair bacmid. These results prove that the N-terminal domain is critical for nuclear transportation of E25 and possibly to its position on the cytoplasm membrane as well; and the sequence downstream of the N-terminal domain also affects trafficking and nuclear localization of the protein. In cells transfected with bacmids containing both the native e25 and individual e25-egfp mutants, the E25-EGFP fusion proteins co-localized with E25 individually, showing similar patterns of subcellular localization as E25 mutants in the absence of native E25 in most cases, suggesting that the E25 likely exists and functions as dimmers or polymers. Production of infectious BV was dramatically reduced and even completely eliminated in most cases, either in the absence or presence of the native e25.

Generation and Biological Characterization of a Neutralization-Resistant Mutant of Newcastle Disease Virus

A neutralization-resistant mutant of Newcastle disease virus (NDV) Kr005 strain belonging to class II genotype VII was generated using a neutralizing monoclonal antibody and its biological effects were assessed. The mutant showed single amino acid substitution (E to K) at position 347 of the hemagglutinin-neuraminidase (HN) protein (E347K mutant). The E347K mutant exhibited marked rounding of the cells and few syncytia in infected chicken embryofibroblast (CEF) cells. The hemadsorption and neuraminidase activities of the E347K mutant of the wild-type virus were 118% and 166%, respectively. The mutant produced a rapid elution pattern whereas the wild type had a slow elution pattern. Growth kinetics studies showed that the E347K mutant produced an 80-times higher yield of extracellular virus in CEF cells compared with the wild-type virus. The time-course virus titer showed a marked increase in mutant-infected cells from 6 h to 12 h post infection (pi), which was consistent with the titer pattern time-course for NA activity. The E347K mutant virus showed a slight decrease in virulence compared to the wild-type virus, but there was no change in pathotype when measured by in vivo pathogenicity testing. These results suggest that an E347K mutation in HN protein might be associated with increased NA activity and subsequent enhancement of virus release from infected cells without change in viral pathotype.

Cellular ESCRT complex and its roles in enveloped viruses budding / 生物工程学报

In eukaryotic cells, multivesicular bodies (MVBs) are required for trafficking of membrane proteins to lysosomes for selective destruction. The sorting of ubiquitylated membrane proteins into multivesicular bodies and the biogenesis of MVBs are mediated by the endosomal sorting complex required for transport (ESCRT). Topologically equivalent to the budding of intralumenal vesicles from the limiting membrane of the MVBs, the ESCRT complex is also involved in cytokinetic abscission, phagophore formation, and enveloped virus budding. Many retroviruses and RNA viruses encode "late-domain" motifs that are able to interact with the components of the ESCRT complex, and the interactions recruit ESCRT-III and VPS4 to the viral assembly and budding sites. Recently, few studies revealed that the ESCRT complex is also required for efficient egress of some DNA viruses, including Hepatitis B, Herpes simplex virus type-1, and Autographa californica multiple nucleopolyhedrovirus. Further examination of virus-ESCRT interactions should shed light on the detailed mechanism of virus assembly and budding.

Hrs inhibits citron kinase-mediated HIV-1 budding via its FYVE domain

Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a key component of the endosomal sorting complexes required for transport and has been demonstrated to play a regulatory role in endocytosis/exocytosis and the accumulation of internal vesicles in multivesicular bodies. Citron kinase is a Ser/The kinase that we previously reported to enhance human immunodeficiency virus type 1 (HIV-1) virion production. However, the relationship between Hrs and citron kinase in HIV-1 production remains elusive. Here, we report that Hrs interacts with citron kinase via its FYVE domain. Overexpression of Hrs or the FYVE domain resulted in a significant decrease in HIV-1 virion production. Depletion of Hrs by RNA interference in HEK293T cells increased HIV-1 virion production and enhanced the activity of citron kinase. These data suggest that Hrs inhibits HIV-1 production by inhibiting citron kinase-mediated exocytosis.

The role of structural protein Gag and related gene (protein) in late stages of the HIV-1 replication cycle and the inhibitors / 药学学报

The late stages of the HIV-1 replication cycle are important to the overall replication cycle. During the late stages, HIV-1 replication undergoes the processes of assembly, release, and maturation, resulting in the production of a mature virus particle capable of infecting a new target cell. The structural protein Gag and its related gene (protein) play a central role in these pathways. The different regions of Gag worked in concert to drive production of a mature infectious particle through protein-protein, protein-RNA and protein-lipid interactions. The designed drug aimed directly at these stages can efficiently block the maturation and infectivity of HIV-1. In this article, the role of structural protein Gag and related gene (protein) in late stages of the HIV-1 replication cycle and related inhibitors is reviewed.

Role of tegument proteins in herpesvirus assembly and egress

Morphogenesis and maturation of viral particles is an essential step of viral replication. An infectious herpesviral particle has a multilayered architecture, and contains a large DNA genome, a capsid shell, a tegument and an envelope spiked with glycoproteins. Unique to herpesviruses, tegument is a structure that occupies the space between the nucleocapsid and the envelope and contains many virus encoded proteins called tegument proteins. Historically the tegument has been described as an amorphous structure, but increasing evidence supports the notion that there is an ordered addition of tegument during virion assembly, which is consistent with the important roles of tegument proteins in the assembly and egress of herpesviral particles. In this review we first give an overview of the herpesvirus assembly and egress process. We then discuss the roles of selected tegument proteins in each step of the process, i.e., primary envelopment, de-envelopment, secondary envelopment and transport of viral particles. We also suggest key issues that should be addressed in the near future.