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1.
Rev Med Virol ; 34(5): e2581, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39243203

RESUMO

Poxviridae is a diverse family of double-stranded DNA viruses, historically significant for diseases like smallpox caused by variola virus (VARV). These viruses exhibit unique cytoplasmic replication strategies, large genomes encoding numerous proteins, and the ability to cause severe cutaneous and systemic diseases. Recent attention has focused on their neurotropic potential, including mechanisms of CNS invasion, immune-mediated damage, and clinical manifestations such as encephalitis and myelitis. This review synthesises current knowledge on poxvirus neurotropism, highlighting pathophysiological mechanisms and clinical implications.


Assuntos
Infecções por Poxviridae , Poxviridae , Humanos , Poxviridae/fisiologia , Poxviridae/genética , Poxviridae/patogenicidade , Infecções por Poxviridae/virologia , Infecções por Poxviridae/patologia , Animais , Tropismo Viral
2.
Dev Comp Immunol ; 161: 105261, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39241936

RESUMO

Low molecular weight proteins, known as chemokines, facilitate the migration and localization of immune cells to the site of infection and injury. One of the first chemokines identified, CXCL8 functions as a key neutrophil activator, recruiting neutrophils to sites of inflammation. Several viral infections, including zoonotic coronaviruses and poxviruses, have been reported to induce the expression of CXCL8. Dromedary camels are known to harbor several potentially zoonotic pathogens, but critical immune molecules such as chemokines remain unidentified. We report here the identification of CXCL8 from the dromedary camel - the first chemokine identified from camelids. The complete dromedary CXCL8 cDNA sequence as well as the corresponding gene sequence from dromedary and two New World camelids - alpaca and llama were cloned. CXCL8 mRNA expression was relatively higher in PBMC, spleen, lung, intestine, and liver. Poly(I:C) and lipopolysaccharide stimulated CXCL8 expression in vitro, while interferon treatment inhibited it. In vitro infection with potentially zoonotic camelpox virus induced the expression of CXCL8 in camel kidney cells. Toxicological studies on camelids have been limited, and no biomarkers have been identified. Hence, we also evaluated CXCL8 mRNA expression as a potential biomarker to assess heavy metal toxicity in camel kidney cells in vitro. CXCL8 expression was increased after in vitro exposure to heavy metal compounds of cobalt and cadmium, suggesting potential utility as a biomarker for renal toxicity in camels. The results of our study demonstrate that camel CXCL8 plays a significant role in immunomodulatory and induced toxicity responses in dromedary camels.


Assuntos
Camelus , Interleucina-8 , Animais , Interleucina-8/metabolismo , Interleucina-8/genética , Camelus/imunologia , Poli I-C/imunologia , Metais Pesados/toxicidade , Camelídeos Americanos/imunologia , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/veterinária , Clonagem Molecular , Poxviridae/imunologia , Poxviridae/genética , Lipopolissacarídeos/imunologia , Células Cultivadas
3.
J Clin Virol ; 174: 105719, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39146599

RESUMO

The re-emergence of human mpox with the multi-country outbreak and a recent report of borealpox (previously Alaskapox) resulting in one death has heightened awareness of the significance of the Poxviridae family and their zoonotic potential. This review examines various poxviruses affecting humans, with discussion of less commonly encountered Poxviridae members, including pathogenesis, epidemiology, and diagnostic methods. Poxvirus treatment is beyond the intended scope of this review and will not be discussed.


Assuntos
Infecções por Poxviridae , Poxviridae , Humanos , Infecções por Poxviridae/virologia , Infecções por Poxviridae/epidemiologia , Infecções por Poxviridae/diagnóstico , Poxviridae/genética , Poxviridae/classificação , Animais , Surtos de Doenças , Zoonoses Virais/epidemiologia , Zoonoses Virais/virologia , Zoonoses/virologia , Zoonoses/epidemiologia
4.
Cell ; 187(20): 5530-5539.e8, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39197447

RESUMO

Animal and bacterial cells sense and defend against viral infections using evolutionarily conserved antiviral signaling pathways. Here, we show that viruses overcome host signaling using mechanisms of immune evasion that are directly shared across the eukaryotic and prokaryotic kingdoms of life. Structures of animal poxvirus proteins that inhibit host cGAS-STING signaling demonstrate architectural and catalytic active-site homology shared with bacteriophage Acb1 proteins, which inactivate CBASS anti-phage defense. In bacteria, phage Acb1 proteins are viral enzymes that degrade host cyclic nucleotide immune signals. Structural comparisons of poxvirus protein-2'3'-cGAMP and phage Acb1-3'3'-cGAMP complexes reveal a universal mechanism of host nucleotide immune signal degradation and explain kingdom-specific additions that enable viral adaptation. Chimeric bacteriophages confirm that animal poxvirus proteins are sufficient to evade immune signaling in bacteria. Our findings identify a mechanism of immune evasion conserved between animal and bacterial viruses and define shared rules that explain host-virus interactions across multiple kingdoms of life.


Assuntos
Evasão da Resposta Imune , Proteínas Virais , Animais , Proteínas Virais/metabolismo , Proteínas Virais/química , Humanos , Bacteriófagos/imunologia , Transdução de Sinais , Poxviridae/imunologia , Poxviridae/genética , Interações Hospedeiro-Patógeno/imunologia , Bactérias/imunologia , Bactérias/metabolismo
5.
Gene ; 927: 148759, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38992761

RESUMO

Ankyrin repeat is a 33-amino acid motif commonly observed in eukaryotes and, to a lesser extent, in prokaryotes and archaea and rarely in viruses. This motif plays a crucial role in regulating various cellular processes like the cell cycle, transcription, cell signaling, and inflammatory responses through interactions between proteins. Poxviruses exhibit a distinctive feature of containing multiple ankyrin repeat proteins within their genomes. All the genera of poxviruses possess these proteins except molluscipox virus, crocodylidpox virus, and red squirrel poxvirus. An intriguing characteristic has generated notable interest in studying the functions of these proteins within poxvirus biology. Within poxviruses, ankyrin repeat proteins exhibit a distinct configuration, featuring ankyrin repeats in the N-terminal region and a cellular F-box homolog in the C-terminal region, which enables interactions with the cellular Skp, Cullin, F-box containing ubiquitin ligase complex. Through the examination of experimental evidences and discussions from current literature, this review elucidates the organization and role of ankyrin repeat proteins in poxviruses. Various research studies have highlighted the significant importance of these proteins in poxviral pathogenesis and, acting as factors that enhance virulence. Consequently, they represent viable targets for developing genetically altered viruses with decreased virulence, thus displaying potential as candidates for vaccines and antiviral therapeutic development contributing to safer and more effective strategies against poxviral infections.


Assuntos
Repetição de Anquirina , Genoma Viral , Poxviridae , Proteínas Virais , Repetição de Anquirina/genética , Poxviridae/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Humanos , Infecções por Poxviridae/virologia
6.
Antiviral Res ; 228: 105943, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38909959

RESUMO

Poxviruses gained international attention due to the sharp rise in monkeypox cases in recent years, highlighting the urgent need for the development of a secure and reliable vaccine. This study involved the development of an innovative combined subunit vaccine (CSV) targeting poxviruses, with lumpy skin disease virus (LSDV) serving as the model virus. To this end, the potential sites for poxvirus vaccines were fully evaluated to develop and purify four recombinant proteins. These proteins were then successfully delivered to the dermis in a mouse model by utilizing dissolvable microneedle patches (DMPs). This approach simplified the vaccination procedure and significantly mitigated the associated risk. CSV-loaded DMPs contained four recombinant proteins and a novel adjuvant, CpG, which allowed DMPs to elicit the same intensity of humoral and cellular immunity as subcutaneous injection. Following immunization with SC and DMP, the mice exhibited notable levels of neutralizing antibodies, albeit at a low concentration. It is noteworthy that the CSV loaded into DMPs remained stable for at least 4 months at room temperature, effectively addressing the storage and transportation challenges. Based on the study findings, CSV-loaded DMPs are expected to be utilized worldwide as an innovative technique for poxvirus inoculation, especially in underdeveloped regions. This novel strategy is crucial for the development of future poxvirus vaccines.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Poxviridae , Poxviridae , Vacinas de Subunidades Antigênicas , Animais , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Infecções por Poxviridae/prevenção & controle , Infecções por Poxviridae/imunologia , Feminino , Poxviridae/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Camundongos Endogâmicos BALB C , Vírus da Doença Nodular Cutânea/imunologia , Vacinação , Imunidade Celular , Imunidade Humoral , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/administração & dosagem , Adjuvantes de Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem
7.
Nat Struct Mol Biol ; 31(7): 1001-1003, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38890551
8.
Annu Rev Immunol ; 42(1): 551-584, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941604

RESUMO

Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.


Assuntos
Evasão da Resposta Imune , Infecções por Poxviridae , Poxviridae , Humanos , Poxviridae/imunologia , Poxviridae/fisiologia , Animais , Infecções por Poxviridae/imunologia , Citocinas/metabolismo , Transdução de Sinais , Proteínas Virais/metabolismo , Proteínas Virais/imunologia , Apresentação de Antígeno/imunologia , Interações Hospedeiro-Patógeno/imunologia
9.
J Infect Public Health ; 17(7): 102470, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38865776

RESUMO

BACKGROUND: Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases. METHODS: The present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level. RESULTS: Three multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses. CONCLUSIONS: Taken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.


Assuntos
Biologia Computacional , Epitopos de Linfócito T , Poxviridae , Vacinas Virais , Vacinas Virais/imunologia , Poxviridae/imunologia , Poxviridae/genética , Biologia Computacional/métodos , Epitopos de Linfócito T/imunologia , RNA Polimerases Dirigidas por DNA/imunologia , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , Modelos Moleculares , Animais , Humanos , Infecções por Poxviridae/prevenção & controle , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/virologia , Epitopos de Linfócito B/imunologia , Simulação de Acoplamento Molecular , Imunoinformática
10.
BMC Infect Dis ; 24(1): 483, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730352

RESUMO

BACKGROUND: Monkeypox (Mpox) is an important human pathogen without etiological treatment. A viral-host interactome study may advance our understanding of molecular pathogenesis and lead to the discovery of suitable therapeutic targets. METHODS: GEO Expression datasets characterizing mRNA profile changes in different host responses to poxviruses were analyzed for shared pathway identification, and then, the Protein-protein interaction (PPI) maps were built. The viral gene expression datasets of Monkeypox virus (MPXV) and Vaccinia virus (VACV) were used to identify the significant viral genes and further investigated for their binding to the library of targeting molecules. RESULTS: Infection with MPXV interferes with various cellular pathways, including interleukin and MAPK signaling. While most host differentially expressed genes (DEGs) are predominantly downregulated upon infection, marked enrichments in histone modifiers and immune-related genes were observed. PPI analysis revealed a set of novel virus-specific protein interactions for the genes in the above functional clusters. The viral DEGs exhibited variable expression patterns in three studied cell types: primary human monocytes, primary human fibroblast, and HeLa, resulting in 118 commonly deregulated proteins. Poxvirus proteins C6R derived protein K7 and K7R of MPXV and VACV were prioritized as targets for potential therapeutic interventions based on their histone-regulating and immunosuppressive properties. In the computational docking and Molecular Dynamics (MD) experiments, these proteins were shown to bind the candidate small molecule S3I-201, which was further prioritized for lead development. RESULTS: MPXV circumvents cellular antiviral defenses by engaging histone modification and immune evasion strategies. C6R-derived protein K7 binding candidate molecule S3I-201 is a priority promising candidate for treating Mpox.


Assuntos
Interações Hospedeiro-Patógeno , Monkeypox virus , Vaccinia virus , Proteínas Virais , Humanos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Vaccinia virus/genética , Vaccinia virus/metabolismo , Células HeLa , Monkeypox virus/genética , Mpox/virologia , Mapas de Interação de Proteínas , Perfilação da Expressão Gênica , Simulação de Acoplamento Molecular , Poxviridae/genética , Poxviridae/metabolismo , Fibroblastos/virologia , Fibroblastos/metabolismo
11.
PLoS One ; 19(5): e0300778, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758816

RESUMO

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.


Assuntos
Simulação de Dinâmica Molecular , Monkeypox virus , Humanos , Monkeypox virus/imunologia , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Simulação por Computador , Poxviridae/imunologia , Vacinas Virais/imunologia , Mapeamento de Epitopos , Mpox/prevenção & controle , Mpox/imunologia , Animais , Receptor 8 Toll-Like/imunologia
12.
Adv Exp Med Biol ; 1451: 21-33, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801569

RESUMO

In the last 4 years, the world has experienced two pandemics of bat-borne viruses. Firstly, in 2019 the SARS-CoV-2 pandemic started and has been causing millions of deaths around the world. In 2022, a Monkeypox pandemic rose in various countries of the world. Those pandemics have witnessed movements and initiatives from healthcare and research institutions to establish a worldwide understanding to battle any future pandemics and biological threats. One Health concept is a modern, comprehensive, unifying ways to improve humans, animals, and ecosystems' health. This concept shows how much they are intertwined and related to one another, whether it is an environmental, or a pathological relation. This review aims to describe Poxviridae and its impact on the One Health concept, by studying the underlying causes of how poxviruses can affect the health of animals, humans, and environments. Reviewing the effect of disease transmission between animal to human, human to human, and animal to animal with pox viruses as a third party to achieve a total understanding of infection and viral transmission. Thus, contributing to enhance detection, diagnosis, research, and treatments regarding the application of One Health.


Assuntos
Saúde Única , Infecções por Poxviridae , Poxviridae , Humanos , Animais , Infecções por Poxviridae/virologia , Infecções por Poxviridae/transmissão , Infecções por Poxviridae/epidemiologia , Poxviridae/fisiologia , Poxviridae/patogenicidade , Poxviridae/genética , COVID-19/virologia , COVID-19/transmissão , COVID-19/epidemiologia , Zoonoses/virologia , Zoonoses/transmissão , Zoonoses/epidemiologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Pandemias , Zoonoses Virais/transmissão , Zoonoses Virais/virologia , Zoonoses Virais/epidemiologia
13.
Adv Exp Med Biol ; 1451: 35-54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801570

RESUMO

Poxvirus assembly has been an intriguing area of research for several decades. While advancements in experimental techniques continue to yield fresh insights, many questions are still unresolved. Large genome sizes of up to 380 kbp, asymmetrical structure, an exterior lipid bilayer, and a cytoplasmic life cycle are some notable characteristics of these viruses. Inside the particle are two lateral bodies and a protein wall-bound-biconcave core containing the viral nucleocapsid. The assembly progresses through five major stages-endoplasmic reticulum (ER) membrane alteration and rupture, crescent formation, immature virion formation, genome encapsidation, virion maturation and in a subset of viruses, additional envelopment of the virion prior to its dissemination. Several large dsDNA viruses have been shown to follow a comparable sequence of events. In this chapter, we recapitulate our understanding of the poxvirus morphogenesis process while reviewing the most recent advances in the field. We also briefly discuss how virion assembly aids in our knowledge of the evolutionary links between poxviruses and other Nucleocytoplasmic Large DNA Viruses (NCLDVs).


Assuntos
Poxviridae , Montagem de Vírus , Poxviridae/genética , Poxviridae/fisiologia , Montagem de Vírus/genética , Humanos , Genoma Viral , Vírion/genética , Vírion/ultraestrutura , Animais , Evolução Molecular , Retículo Endoplasmático/virologia
14.
Adv Exp Med Biol ; 1451: 205-217, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801580

RESUMO

The family Poxviridae is a large family of viruses with a ubiquitous distribution, subdivided into two subfamilies: Chordopoxvirinae (poxviruses of vertebrates) and Entomopoxvirinae (poxviruses of insects). Only three species from the first subfamily, Orthopoxvirus (OPV), Molluscipoxvirus and Parapoxvirus, can infect the human being. In the paediatric population, viruses belonging to the first two subfamilies have the greatest importance. Following the eradication of smallpox in 1980, vaccination of the general population was discontinued after careful consideration of the risks and benefits. However, nearly all children and most of the world's population had little to no protection against OPV. The aim of this chapter is to review the current evidence on the aetiology, clinical manifestations, diagnosis and management of Poxviridae infections in children.


Assuntos
Infecções por Poxviridae , Poxviridae , Humanos , Criança , Infecções por Poxviridae/virologia , Infecções por Poxviridae/epidemiologia , Infecções por Poxviridae/diagnóstico , Poxviridae/classificação , Poxviridae/genética , Poxviridae/patogenicidade , Pré-Escolar , Lactente , Animais
15.
Adv Exp Med Biol ; 1451: 239-252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801582

RESUMO

Although WHO-led global efforts led to eradication of smallpox over four decades ago, other poxviruses, especially monkeypox, have re-emerged to occupy the ecological niche vacated by smallpox. Many of these viruses produce similar lesions thus mandating a prompt laboratory confirmation. There has been considerable evolution in the techniques available to diagnose these infections and differentiate between them. With the 2022 multi-country outbreak of monkeypox, significant efforts were made to apprise the laboratory diagnosis of the virus and numerous real-time-PCR-based assays were made commercially available. This chapter discusses the sample collection and biosafety aspects along with the repertoire of diagnostic modalities, both traditional and emerging, for poxviruses which a special focus on monkeypox. The advantages and disadvantages of each technique have been illustrated. We have also reflected upon the newer advances and the existing lacunae.


Assuntos
Infecções por Poxviridae , Humanos , Infecções por Poxviridae/diagnóstico , Infecções por Poxviridae/virologia , Poxviridae/genética , Poxviridae/isolamento & purificação , Animais , Varíola/diagnóstico , Varíola/virologia , Varíola/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Mpox/diagnóstico , Mpox/virologia , Mpox/epidemiologia
16.
Adv Exp Med Biol ; 1451: 183-204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801579

RESUMO

Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.


Assuntos
Antivirais , Infecções por Poxviridae , Humanos , Animais , Infecções por Poxviridae/tratamento farmacológico , Infecções por Poxviridae/virologia , Infecções por Poxviridae/imunologia , Antivirais/uso terapêutico , Pneumonia Viral/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/complicações , Poxviridae/patogenicidade , Poxviridae/fisiologia , Poxviridae/genética , Vaccinia virus/patogenicidade , Vaccinia virus/fisiologia , Varíola/virologia , Varíola/prevenção & controle , Vírus da Varíola/patogenicidade , Vírus da Varíola/genética
17.
Adv Exp Med Biol ; 1451: 273-287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801584

RESUMO

Smallpox was a significant cause of mortality for over three thousand years, amounting to 10% of deaths yearly. Edward Jenner discovered smallpox vaccination in 1796, which rapidly became a smallpox infection preventive practice throughout the world and eradicated smallpox infection by 1980. After smallpox eradication, monkeypox vaccines have been used primarily in research and in outbreaks in Africa, where the disease is endemic. In the present, the vaccines are being used for people who work with animals or in high-risk areas, as well as for healthcare workers treating patients with monkeypox. Among all orthopoxviruses (OPXV), monkeypox viral (MPXV) infection occurs mainly in cynomolgus monkeys, natural reservoirs, and occasionally causes severe multi-organ infection in humans, who were the incidental hosts. The first case of the present epidemic of MXPV was identified on May 7, 2022, and rapidly increased the number of cases. In this regard, the WHO declared the outbreak, an international public health emergency on July 23, 2022. The first monkeypox vaccine was developed in the 1960s by the US Army and was based on the vaccinia virus, which is also used in smallpox vaccines. In recent years, newer monkeypox vaccines have been developed based on other viruses such as Modified Vaccinia Ankara (MVA). These newer vaccines are safer and can provide longer-lasting immunity with fewer side effects. For the future, there is ongoing research to improve the current vaccines and to develop new ones. One notable advance has been the development of a recombinant vaccine that uses a genetically modified vaccinia virus to express monkeypox antigens. This vaccine has shown promising results in pre-clinical trials and is currently undergoing further testing in clinical trials. Another recent development has been the use of a DNA vaccine, which delivers genetic material encoding monkeypox antigens directly into cells. This type of vaccine has shown effectiveness in animal studies and is also undergoing clinical testing in humans. Overall, these recent advances in monkeypox vaccine development hold promise for protecting individuals against this potentially serious disease.


Assuntos
Vacina Antivariólica , Humanos , Animais , Vacina Antivariólica/imunologia , Varíola/prevenção & controle , Varíola/imunologia , Varíola/epidemiologia , Varíola/história , História do Século XXI , História do Século XX , Mpox/prevenção & controle , Mpox/epidemiologia , Mpox/imunologia , Infecções por Poxviridae/prevenção & controle , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/epidemiologia , Poxviridae/imunologia , Poxviridae/genética , Monkeypox virus/imunologia , Monkeypox virus/genética , Vacinação , Vacinas Virais/imunologia , Desenvolvimento de Vacinas
18.
Adv Exp Med Biol ; 1451: 369-381, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801591

RESUMO

Despite the significant advancement of new tools and technology in the field of medical biology and molecular biology, the challenges in the treatment of most cancer types remain constant with the problem of developing resistance toward drugs and no substantial enhancement in the overall survival rate of cancer patients. Immunotherapy has shown the most promising results in different clinical and preclinical trials in the treatment of various cancer due to its higher efficacy and minimum collateral damage in many cancer patients as compared to conventional chemotherapy and radiotherapy. An oncolytic virus is a new class of immunotherapy that can selectively replicate in tumor cells and destroy them by the process of cell lysis while exerting minimum or no effect on a normal cell. Besides this, it can also activate the host's innate immune system, which generates an anti-tumor immune response to eliminate the tumor cells. Several wild types and genetically modified viruses have been investigated to show oncolytic behavior. Vaccinia virus has been studied extensively and tested for its promising oncolytic nature on various model systems and clinical trials. Recently, several engineered vaccinia viruses have been developed that express the desired genes encoded for selective penetration in tumor cells and enhanced activation of the immune system for generating anti-tumor immunity. However, further investigation is required to prove their potential and enhance their therapeutic efficacy.


Assuntos
Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Poxviridae , Humanos , Terapia Viral Oncolítica/métodos , Neoplasias/terapia , Neoplasias/imunologia , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologia , Animais , Poxviridae/genética , Poxviridae/fisiologia , Imunoterapia/métodos , Vaccinia virus/genética , Vaccinia virus/imunologia , Vaccinia virus/fisiologia
19.
Adv Exp Med Biol ; 1451: 337-354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801589

RESUMO

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4+ T cells, CD4+ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.


Assuntos
Antivirais , Infecções por Poxviridae , Poxviridae , Humanos , Infecções por Poxviridae/tratamento farmacológico , Infecções por Poxviridae/virologia , Infecções por Poxviridae/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Poxviridae/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/química , Terapias Complementares/métodos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química
20.
Adv Exp Med Biol ; 1451: 331-336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801588

RESUMO

Poxviruses belong to the family of double-stranded DNA viruses, and it is pathogenic for humans and spread worldwide. These viruses cause infections and various diseases in human. So, it is required to develop new drugs for the treatment of smallpox or other poxvirus infections. Very few potential compounds for the treatment of poxvirus such as smallpox, chickenpox, and monkeypox have been reported. Most of the compounds has used as vaccines. Cidofovir is most commonly used as a vaccine for the treatment of poxviruses. There are no phytochemicals reported for the treatment of poxviruses. Very few phytochemicals are under investigation for the treatment of poxviruses.


Assuntos
Antivirais , Poxviridae , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Poxviridae/efeitos dos fármacos , Poxviridae/fisiologia , Poxviridae/genética , Animais , Infecções por Poxviridae/tratamento farmacológico , Infecções por Poxviridae/virologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química
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