Nota Técnica N. 2/2022 - SES/ASREA - 18776 - Nota técnica de manejo da Monkeypox em gestantes, puérperas e lactantes / Technical Note N. 2/2022 - SES/ASREA- 18776 - Technical note on the management of Monkeypox in pregnant, postpartum and lactating women

A presente nota técnica tem como objetivo orientar os profissionais de saúde em relação à condução dos casos suspeitos e/ou confirmados de Monkeypox em gestantes, puérperas e lactantes. A Monkeypox (MPX) ou Varíola M é uma doença causada pelo vírus Monkeypox do gênero Orthopoxvirus e família Poxviridae. Trata-se de uma zoonose viral cuja transmissão pode ocorrer por meio do contato desprotegido com lesões ou fluidos corporais (contato sexual, saliva, olhos, cavidade oral) e/ou materiais contaminados (roupa de cama, vestes, utensílios domésticos)

This technical note aims to guide health professionals in relation to the management of suspected and/or confirmed cases of Monkeypox in pregnant, postpartum and lactating women. Monkeypox (MPX) or Smallpox M is a disease caused by the Monkeypox virus of the genus Orthopoxvirus and family Poxviridae. It is a viral zoonosis whose transmission can occur through unprotected contact with injuries or bodily fluids (sexual contact, saliva, eyes, sinus oral) and/or contaminated materials (bedding, clothing, household items)

Volta ás aulas - Monkeypox - varíola símia / Back to School - Monkeypox - simian smallpox

A Monkeypox pertence ao mesmo vírus da família (Poxviridae) varíola. É transmitida de pessoa a pessoa. O macaco não tem participação na transmissão para humanos. Até o momento, sabe-se que na África os casos mais severos ocorreram com mais frequência em crianças. Recentemente, três crianças foram diagnosticadas com Monkeypox na cidade de São Paulo (SP) e a rápida progressão da doença indica uma alta probabilidade de mais casos nesta faixa etária em outras regiões do país

Monkeypox belongs to the same virus in the smallpox family (Poxviridae). It is transmitted from person to person. The monkey has no role in transmission to humans. So far, it is known that in Africa the most severe cases occurred more frequently in children. Recently, three children were diagnosed with Monkeypox in the city of São Paulo (SP) and the rapid progression of the disease indicates a high probability of more cases in this age group in other regions of the country

Vaccinia zoonótica en Colombia: evidencia acumulativa de la emergencia de los poxvirus en el mundo / Zoonotic vaccinia in Colombia: Cumulative evidence of the emergence of poxviruses in the world

RESUMEN La reciente ocurrencia de infecciones por el virus vaccinia en animales y humanos en distintos lugares de la geografía colombiana, sumadas a otras por éste y por otros virus pertenecientes al género Orthopoxvirus (familia Poxviridae), ocurridas en algunos países de Suramérica, África, Asia y Europa se convierten en evidencia de la inminente emergencia y re-emergencia de este género, con características biológicas y epidemiológicas que le confieren gran interés para la salud pública del mundo, como lo fue en el pasado una de sus especies representativas: el virus de la viruela. Esta emergencia y re-emergencia parecen estar relacionadas con la suspensión en las décadas de los 70s y 80s de las campañas de vacunación contra la viruela, las cuales; insospechadamente estuvieron protegiendo a la población, no únicamente contra este virus, sino contra otros del mismo género. En el presente artículo se hace una revisión de la biología y epidemiología de los principales miembros del género Orthopoxvirus, su presentación clínica, antecedentes históricos, contexto social, e impacto en la salud pública mundial en el pasado, presente y a futuro.(AU)

ABSTRACT The recent occurrence of vaccinia virus infections in humans and animals in Colombia, together with that reported for this and other species of the genus Orthopoxvirus in some South American, African, Asian and European countries, is supporting evidence of the emergence and re-emergence of the genus. This fact has become of great interest for public health around the world due to its biological and an epidemiological features, as was in the past the variola virus, one of its representatives. The emergence and re-emergence of the genus Orthopoxvirus may be a consequence of stopping vaccination against the variola virus in the 1970s and 1980s. This vaccination unsuspectedly induced cross-protective immunity to other species of that genus. This is a review of the history, biology and epidemiology of the main species of the genus Orthopoxvirus, together with its clinical presentation, social context and public health impact in the past, present and future.(AU)

First phylogenetic analysis of avipoxvirus (APV) in Brazil / Primeira análise filogenética de avipoxvirus (APV) no Brasil

This study represents the first phylogenetic analysis of avian poxvirus recovered from turkeys in Brazil. The clinical disorders related to fowlpox herein described occurred in a turkey housing system. The birds displaying characteristic pox lesions which were observed on the neck, eyelids and beak of the turkeys. Four affected turkeys were randomly chosen, euthanized and necropsied. Tissues samples were submitted for histopathological analysis and total DNA was further extracted, amplified by conventional PCR, sequenced and phylogenetically analyzed. Avian poxviruses specific PCR was performed based on P4b core protein gene sequence. The histological analysis revealed dermal inflammatory process, granulation tissue, hyperplasia of epithelial cells and inclusion bodies. The P4b gene was detected in all samples. Sequencing revealed a 100% nucleotide and amino acid sequence identity among the samples, and the sequences were deposited in GenBank®. The four Avian poxviruses fragments sequenced in this study clustered along the A1 clade of avipoxviruses, and were classified as Avipoxvirus (APV). Additional studies, such as virus isolation, PCR and sequencing includinga large number of specimens from the Brazilian turkey production must be conducted due to the hazardous risk that poxvirus infections may cause to the Brazilian poultry production scenario, given that Brazil's turkey production attracts attention due to its economic importance worldwide. Our findings point to the need to identify the prevalence of APV in Brazilian turkey production, to perform risk assessment studies and continued surveillance of APV infections in both wild and commercial avian species.

Este trabalho representa a primeira análise filogenética de Poxvirus aviário detectado em perus no Brasil. Os distúrbios clínicos relacionados com bouba aviária aqui descritos ocorreram em um sistema de alojamento de perus. As aves apresentaram lesões características de varíola observadas no pescoço, pálpebras e bico das aves. Quatro perus com sinais característicos foram escolhidos aleatoriamente, sacrificados e submetidos à autópsia. Amostras de tecido foram submetidas à análise histopatológica e o DNA total foi extraído, amplificado por PCR convencional e os amplicons foram sequenciados e analisados ​​filogeneticamente. A PCR específica para Poxvírus aviário foi realizada com base na seqüência do gene da proteína do núcleo P4b. A análise histológica revelou um processo inflamatório dérmico, tecido de granulação, hiperplasia de células epiteliais e corpúsculos de inclusão. O gene P4b foi detectado em todas as amostras. O sequenciamento revelou uma identidade entre nucleotídeos e aminoácido de 100% entre as amostras e as sequências foram depositadas no GenBank®. Os quatro fragmentos de poxvírus aviário sequenciado neste estudo foram agrupados no clado A1 de avipoxvirus e foram classificados como Avipoxvirus (APV). Estudos adicionais, como isolamento viral, PCR e sequenciamento, incluindo um grande número de perus da produção brasileira devem ser conduzidos devido ao grave risco que a infecção por poxvírus pode causar ao cenário de produção avícola brasileira, tendo em vista que a produção brasileira de perus atrai atenção devido a sua importância mundial. Nossos resultados apontam para a necessidade de identificar a prevalência da APV na produção de peru no Brasil, para realizar estudos de avaliação de risco e continuada monitoração de infecções por APV nas espécies de aves comerciais e silvestres.

Progress on host range factors and their mechanisms of poxvirus / 病毒学报

Poxvirus is one of the most serious zoonosis pathogens, which has largest genome and broadest host spectrum. With the development of molecular biology, functional genomics, and immunology-related technology, the interactions between pathogen and the host, particularly a large array of host range factors and their functions have been increasingly discovered. These findings provide references for the molecular basis of poxvirus tissue tropism and host specificity. This review focus on the introduction of host range factors in major members of Chordopoxvirinae to highlight the understanding of the mechanisms of molecular genetic evolution, the host tropism, and cross-species infection of poxviruses.

Viral vectors for vaccine applications

Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast number of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense.

Vacina experimental produzida em cultivo celular confere proteção parcial contra o ectima contagioso em ovinos / Experimental vaccine produced in tissue culture confers partial protection against contagious ecthyma in sheep

O ectima contagioso (também conhecido como orf), é uma doença debilitante de ovinos e caprinos causada pelo vírus do orf (ORFV). A vacinação tem sido usada com relativo sucesso no controle da doença. No entanto, as vacinas atuais contêm amostras virulentas do agente, são produzidas por escarificação cutânea de animais, e apresentam eficácia questionável. Assim, o presente trabalho teve como objetivo produzir e testar a eficácia de uma vacina experimental produzida em cultivo celular. A cepa IA-82 do ORFV foi submetida a 21 passagens em cultivo de células BHK-21 e usada para vacinar ovinos jovens (n=30), por escarificação cutânea na face interna da coxa. A vacinação produziu pústulas e crostas em 16 dos 30 ovinos vacinados, indicando imunização adequada. Noventa dias após a vacinação, ovinos vacinados (n=16) e controles (n=16) foram inoculados com uma cepa virulenta do ORFV (10(6,9)DICC50/mL) após escarificação na comissura labial. Todos os animais desenvolveram lesões típicas de ectima, incluindo hiperemia, vesículas, pústulas e crostas. No entanto, os animais vacinados desenvolveram lesões mais leves e passageiras do que os controles, e os escores clínicos foram estatisticamente diferentes (p<0,05) entre os dias 10 e 22 pós-desafio. Além disso, o tempo de duração da doença foi significativamente inferior (p<0,05) nos animais vacinados. Os animais vacinados também excretaram menor quantidade de vírus (p<0,05) e por um período significativamente mais curto do que os controles (13 dias versus 22 dias, p<0,001). Esses resultados demonstram a proteção parcial conferida pela vacina experimental e, dependendo da melhoria dos índices de imunização e proteção, são promissores no sentido da utilização de vacinas contra o ORFV produzidas em cultivo celular.

Contagious ecthyma, also known as orf, is a debilitating disease of sheep and goats caused by the parapoxvirus, orf virus (ORFV). Vaccination has been used with relative success to reduce the losses caused by the disease, yet the current vaccines contain virulent virus, are empirically produced through skin scarification of live lambs, and present questionable efficacy. Therefore, the present study aimed at developing and testing an experimental ORFV vaccine produced in tissue culture. The ORFV strain IA-82 was submitted to 21 passages in BHK-21 cells and then used to immunize lam bs (n=30) through skin scarification of the internal face of the hind limb. Vaccination produced localized pustules and scabs lesions in 16 out of 30 animals, indicating an adequate replication of the vaccine virus. Ninety days after vaccination, vaccinated (n=16) and control lambs (n=16) were inoculated with a virulent ORFV strain (10(6,9)TCID50/ml) in the labial commissure. Vaccinated and control lambs developed typical orf lesions, characterized by hyperemia, vesicles, pustules and scab formation. Nonetheless, vaccinated animals developed milder lesions compared to controls and the clinical scores were significantly lower (p<0.05) between days 10 and 22 post-challenge. In addition, the mean duration of clinical disease was significantly reduced in vaccinated animals (p<0.05). Furthermore, vaccinated animals excreted much less virus (p<0.05) and for a significantly shorter period of time than did the controls (13 days versus 22 days, p<0.001). These results demonstrate partial protection by the experimental vaccine and, upon improvement of immunization and protection indices, are promising towards the use of tissue culture-based ORFV vaccines.

Regulation of NF-kappaB signaling pathway by poxvirus / 病毒学报

Poxviruses, a type of ds-DNA viruses which mainly target at the epithelial cell, are the pathogens of human and animals. During the revolution of poxviruses, the viruses encode multiple proteins that regulate the immune system to monitor the viral reproductive cycle in host cells. The nuclear kappa B (NF-kappaB) pathway is essential to signal transcription in the innate immune system. Therefore, poxviruses have adopted different strategies to elude immune detection and destruction regulated by NF-kappaB. Further research in this field would help us develop preventive and therapeutic preparation for pox. Given the renewed interest in poxvirus, we review the current understanding of how the various classes of poxviralimmunomodulatory proteins target and manipulate the NF-kappaB pathway.

Poxvirus que causan enfermedad en los seres humanos / Poxviruses that cause human disease

Los poxvirus se dividen en dos subfamilias: la Cordopoxvirinae con ocho géneros que infectan tanto a mamíferos como a aves, y la Entomopoxvirinae con tres géneros que sólo afectan a los insectos. Los poxvirus que infectan a los humanos se distribuyen en cuatro géneros pertenecientes a la familia Cordopoxvirinae, entre los que se incluyen los Orthopoxvirus, Parapoxvirus, Molluscipoxvirus y Yatapoxvirus. De forma interesante, todos los anteriores géneros producen lesiones cutáneas con especiales características. En este artículo se revisan la microbiología, la patogénesis, la inmunidad, la epidemiología, las manifestaciones clínicas e histopatológicas de estos virus, y su tratamiento.

A mouse model based on replication-competent Tiantan vaccinia expressing luciferase/HIV-1 Gag fusion protein for the evaluation of protective efficacy of HIV vaccine / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Developing an effective vaccine against human immunodeficiency virus type 1 (HIV-1) remains a grand challenge after more than two decades of intensive effort. It is partially due to the lack of suitable animal models for screening and prioritizing vaccine candidates. In this study, we aim to develop a mice model to test HIV-1 vaccine efficacy.</p><p><b>METHODS</b>We constructed a recombinant vaccinia expressing firefly luciferase and HIV-1 Gag fusion protein based on Tiantan strain, an attenuated but replication-competent poxvirus (rTTV-lucgag). By quantifying the luciferase activity as its read out, we defined the biodistribution of Tiantan strain poxvirus in mice inoculated intraperitoneally and attempted to apply this model to evaluate the HIV-1 vaccine efficacy.</p><p><b>RESULTS</b>Our data demonstrated that the rTTV-lucgag was able to express high level of luciferase (< or = 10(6) relative luciferase units (RLU)/mg protein) and HIV-1 Gag (> 3 folds increase comparing to the control). After intraperitoneal inoculation, this virus had dominant replication in the ovary, uterus, and cervix of mice and the luciferase activities in those organs are significantly correlated with viral titers (r(2) = 0.71, P < 0.01). Pre-immunization with an HIV gag DNA vaccine reduced the luciferase activity in ovary from (6006 +/- 3141) RLU/mg protein in control group to (1538 +/- 463) RLU/mg protein in vaccine group (P = 0.1969).</p><p><b>CONCLUSIONS</b>The luciferase activity in ovary could represent viral replication in vivo; this rTTV-lucgag/mice model may be suitable to assess the protective efficacy of cytotoxic T-cell responses to HIV Gag with less tedious work and high through-put.</p>

Recombinant viruses as vaccines against viral diseases

Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

The Gamma Herpesvirus Alcelaphine Herpesvirus 1 Causes Apoptotic Infection in Permissive Cell Lines

Apoptosis is a host defense mechanism that the cell uses to limit production of infectious virus. Although many viruses can induce apoptosis in infected cells, large DNA viruses, such as poxviruses, herpesviruses and adenoviruses, usually exhibit the ability to suppress the induction of apoptosis in the infected cells. Several publications have attested to the ability of herpesviruses to protect cells against apoptosis. We investigated the ability of the virus to protect cells in continuous cultivation from apoptosis induced by the virus itself. The gamma herpesvirus alcelaphine herpesvirus 1 (AlHV-1) has been shown to harbor genes with antiapoptotic potentialities. However, here we have demonstrated that productive infection of adherent, permissive cell lines by AlHV-1 resulted in a cytopathic effect characterized by induction of apoptosis. This phenomenon was confirmed using different techniques to detect apoptosis and using different virus strains and cell lines. Therefore, despite the presence of antiapoptotic genes in its genome, AlHV-1 could complete its cycle of productive infection while inducing apoptosis of infected cells. This finding might have implications for the pathobiology of AlHV-1 and other gamma herpesviruses in vivo.

A new concept in prophylaxis and therapy: paramunization by poxvirus inducers

The so-called primitive, innate or paraspecific immune system is the phylogenetically older part of the complex immune system. It enables the organism to immediately attack various foreign substances, infectious pathogens, toxins and transformed cells of the organism itself. "Paramunity" is defined as an optimal regulated and activated, antigen-nonspecific defence, acquired through continuous active and succesful confrontation with endogenous and exogenous noxes or by means of "paramunization" with so called "paramunity inducers". Paramunity inducers based on different pox virus species (e.g. Baypamun®, Duphapind®, Conpind) have turned out to be effective and safe when applied with human beings as well as with animals. Pox virus inducers activate phagocytosis and NK-cells in addition to regulation of various cytokines, notably interferon a and g, IL 1, 2, CSF and TNF which comprise the network of the complex paraspecific immune system. The results of experimental work as well as practical use in veterinary medicine have shown that paramunization by pox inducers goes far beyond the common understanding of so-called ,,immuno-therapy". They are "bioregulators", because they have 1. a regulatory effect on a disturbed immune system in the sense of an optimal homoeostasis, and 2. simultaneously a regulatory effect between the immune, nervous, circulatory and hormone system. Therefore, the use of paramunization by pox inducers opens a new way of prophylaxis and therapy, not only with regard to infections, but also with regard to different other indications

Isolation and characterization of soluble antigens of sheep poxvirus.

A soluble antigen fraction of sheep poxvirus (SPV) isolated from infectious virus particles by ultracentrifugation and purified by subtractive immunoaffinity chromatography was characterized. Exclusion chromatography studies revealed 10 proteins of molecular weight (MW) 220, 168, 87.3, 71.5, 52.5, 36.7, 31.0, 23.4, 18.3 and 14.2 kDa. Nine of them were found to be precipitinogens and 5 were identified as structural components of the virus particles. SDS-PAGE analysis revealed a polypeptide profile of 10 bands with 2 prominent polypeptides of 64 and 42 kDa. Western blotting, however, detected 2 immunogenic polypeptides of MW 100 and 64 kDa. Moreover, crossed immunoelectrophoresis showed the presence of proteins of varied electrophoretic mobility and sharing of antigenic determinants among a few soluble antigens. Physico-chemical characterization further revealed that these precipitinogens can withstand ambient temperatures, but were sensitive to trypsin and ether whereas, chloroform had no effect on immunoprecipitation pattern of soluble antigens.

An Immunohistochemical Study of Molluscum Contagiosum / 대한피부과학회지

BACKGROUND: Molluscum contagiosum is a common viral infect oudisease of the skin and mucous membrane that is caused by a molluscum contagiosum virus(MCV; which belongs to the poxviridae family. One of the characteristic histopathologic findings is an epidermal hyperplasia Porter and Archard reported that this phenomenon might be explained by a virus induced epidermal growth factor (EGF) like polypeptide. There was a report that epidermal prolifeation in viral infection might be modulated by other factors than the virus itself such as local immune response. OBJECTIVE: The purpose of this study was to examine the expression pattern of epidermal growth factor receptor and other immunocompetent cells by immunohistochemical stainings. METHOD : We performed iinmunoperoxidase staining on the 11 slaecmens of formalin-fixed, paraffin-embedded molluscum lesions and 15 specimens of snap frozen mollucum lesions with nine primary antibodies(EGFR, factor XIIIa, CDla, S-100 protein, MAC 387, HLA-IR, CD4, CDS, L26) RESULTS: EGF receptors were strongly expressed in lesional MCV ifect,ed keratinocytes. The number of CDla and factor XIIIa positive dermal dendritic cells were sigtly increased. In inflamed lesions, CD4 and HLA-DR expressions were increased in the dermis and per lesional epidermis. CONCLUSION: This study shows that 1) increased EGFR expression is of MCV infected keratinocytes may be related to the pathogenesis of epidermal hyperplasia. 2) helper T lyrnphocytes may operate in inflamed molluscum lesions.

Polyclonal B-lymphocyte activation of sheep by Mycobacterium phlei against sheep pox virus.

A trypsinized preparation of Mycobacterium phlei, non specific stimulator of immunity (NSI), and Sheep Pox Virus (SPV) were inoculated in different groups of sheep to activate B-lymphocytes and induce SPV neutralizing substance(s). NSI sensitized sheep B-lymphocytes in the presence of NSI or lymphokine elaborated SPV neutralizing substance(s). The SPV sensitized B-lymphocytes also mediated such neutralizing substance(s). Healthy control sheep B-lymphocytes failed to show any appreciable amount of viral neutralizing substance. However, a significant virus neutralizing substance(s) was detected when healthy sheep B-lymphocytes were cultured in presence of NSI antigen along with lymphokines.

Enhanced production of antibody with specific antigen.

On inoculation of nonspecific stimulator of immunity (NSI), prepared from Mycobacterium phlei (M. phlei), simultaneously along with sheep pox virus (SPV) in sheep, the recipient has exhibited appreciable level of SPV specific antibody as early as on 10th day which reached at peak level on 20th day and remained unaltered on 30th day of postimmunisation as evinced by serum neutralisation test (SNT), enzyme linked immunosorbant assay (ELISA) indirect, fluorescent antibody technique (FAT) indirect, counter immunoelectrophoresis (CIEP) and finally by virulent SPV challenge. On the contrary, sheep, when immunised with SPV only could not produce appreciable level of antibody on 10th day but did so on 20th day of inoculation. SPV and NSI immunised sheep produced enhanced protection against virulent SPV challenge in comparison with sheep immunised with SPV only. Healthy control sheep, however, could not resist challenge.

Identification and size variation of terminal fragments of sheep pox virus genome.

Terminal fragments of sheep pox virus DNA identified by snap-back analysis showed terminal covalent cross-links. Southern blot hybridization using a terminal fragment probe confirmed the termini and terminal repeats (common sequences) of the sheep pox virus genome. Terminal fragment length variability was observed between virus isolates.

A comparison of genomes of sheep pox virus isolates.

Sheep pox virus DNAs from field isolates and vaccine strains were analysed by digestion with the restriction enzymes PstI and Bam HI. The restriction profiles generated by these enzymes show very close relationship between isolates from different geographical regions. The patterns of isolates can be grouped by the animal of origin (e.g. a cattle pox isolate can be differentiated from sheep pox isolate). The molecular weights of the genomes of different isolates varied from 91 to 94 MDa. The restriction enzyme patterns can be used as a molecular epidemiological tool for differentiating field and vaccine isolates.