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Infection, Genetics and Evolution :... Nov 2022In the last five years, the prevalence of monkeypox has been increasing both in the regions considered endemic for the disease (West and Central Africa) and worldwide.... (Review)
Review
In the last five years, the prevalence of monkeypox has been increasing both in the regions considered endemic for the disease (West and Central Africa) and worldwide. Indeed, in July 2022, the World Health Organization declared the ongoing global outbreak of monkeypox a public health emergency of international concern. The disease is caused by monkeypox virus (MPXV), a member of the Orthopoxvirus genus, which also includes variola virus (the causative agent of smallpox) and vaccinia virus (used in the smallpox eradication campaign). Here, we review aspects of MPXV genetic diversity and epidemiology, with an emphasis on its genome structure, host range, and relationship with other orthopoxviruses. We also summarize the most recent findings deriving from the sequencing of outbreak MPXV genomes, and we discuss the apparent changing of MPXV evolutionary trajectory, which is characterized by the accumulation of point mutations rather than by gene gains/losses. Whereas the availability of a vaccine, the relatively mild presentation of the disease, and its relatively low transmissibility speak in favor of an efficient control of the global outbreak, the wide host range of MPXV raises concerns about the possible establishment of novel reservoirs. We also call for the deployment of field surveys and genomic surveillance programs to identify and control the MPXV reservoirs in West and Central Africa.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Smallpox; Africa, Central
PubMed: 36202208
DOI: 10.1016/j.meegid.2022.105372 -
Viruses Nov 2023Monkeypox virus (MPXV), belonging to the family and genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and... (Review)
Review
Monkeypox virus (MPXV), belonging to the family and genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFNγ, CC and CXC chemokines, IL-1β, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFNα and IFNβ. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.
Topics: Child; Humans; Female; Pregnancy; Child, Preschool; Aged; Monkeypox virus; Immune Evasion; Vaccination; Corneal Diseases; Eyelids
PubMed: 38140542
DOI: 10.3390/v15122301 -
Viruses Sep 2022(CPXV; genus ; family ) is the causative agent of cowpox, a self-limiting zoonotic infection. CPXV is endemic in Eurasia, and human CPXV infections are associated with...
(CPXV; genus ; family ) is the causative agent of cowpox, a self-limiting zoonotic infection. CPXV is endemic in Eurasia, and human CPXV infections are associated with exposure to infected animals. In the Fennoscandian region, five CPXVs isolated from cats and humans were collected and used in this study. We report the complete sequence of their genomes, which ranged in size from 220-222 kbp, containing between 215 and 219 open reading frames. The phylogenetic analysis of 87 orthopoxvirus strains, including the Fennoscandian CPXV isolates, confirmed the division of CPXV strains into at least five distinct major clusters (CPXV-like 1, CPXV-like 2, VACV-like, VARV-like and ECTV-Abatino-like) and can be further divided into eighteen sub-species based on the genetic and patristic distances. Bayesian time-scaled evolutionary history of CPXV was reconstructed employing concatenated 62 non-recombinant conserved genes of 55 CPXV. The CPXV evolution rate was calculated to be 1.65 × 10 substitution/site/year. Our findings confirmed that CPXV is not a single species but a polyphyletic assemblage of several species and thus, a reclassification is warranted.
Topics: Animals; Humans; Cowpox virus; Phylogeny; Bayes Theorem; Cowpox; Orthopoxvirus; Genomics
PubMed: 36298689
DOI: 10.3390/v14102134 -
Expert Review of Anti-infective Therapy Mar 2021Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in... (Review)
Review
INTRODUCTION
Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in a smallpox outbreak. While there has not been a reported case of smallpox since 1978 it is still considered a serious bioterrorism threat.
AREAS COVERED
A brief history of smallpox from its proposed origins as a human disease through its eradication in the late 20th century is presented. The current smallpox threat and the current public health response plans are described. The discovery, and development of tecovirimat through NDA submission and subsequent approval for treatment of smallpox are discussed. Google Scholar and PubMed were searched over all available dates for relevant publications.
EXPERT OPINION
Approval of tecovirimat to treat smallpox represents an important milestone in biosecurity preparedness. Incorporating tecovirimat into the CDC smallpox response plan, development of pediatric liquid and intravenous formulations, and approval for post-exposure prophylaxis would provide additional health security benefit.Tecovirimat shows broad efficacy against orthopoxviruses in vitro and in vivo and could be developed for use against emerging orthopoxvirus diseases such as monkeypox, vaccination-associated adverse events, and side effects of vaccinia oncolytic virus therapy.
Topics: Antiviral Agents; Benzamides; Bioterrorism; Humans; Isoindoles; Orthopoxvirus; Poxviridae Infections; Smallpox
PubMed: 32882158
DOI: 10.1080/14787210.2020.1819791 -
Clinical Immunology (Orlando, Fla.) Oct 2022Monkeypox is a zoonotic Orthopoxvirus which has predominantly affected humans living in western and central Africa since the 1970s. Type I and II interferon signaling,... (Review)
Review
Monkeypox is a zoonotic Orthopoxvirus which has predominantly affected humans living in western and central Africa since the 1970s. Type I and II interferon signaling, NK cell function, and serologic immunity are critical for host immunity against monkeypox. Monkeypox can evade host viral recognition and block interferon signaling, leading to overall case fatality rates of up to 11%. The incidence of monkeypox has increased since cessation of smallpox vaccination. In 2022, a global outbreak emerged, predominantly affecting males, with exclusive human-to-human transmission and more phenotypic variability than earlier outbreaks. Available vaccines are safe and effective tools for prevention of severe disease, but supply is limited. Now considered a public health emergency, more studies are needed to better characterize at-risk populations and to develop new anti-viral therapies.
Topics: Communicable Diseases; Humans; Interferons; Male; Mpox (monkeypox); Monkeypox virus; Orthopoxvirus; Poxviridae Infections
PubMed: 36067982
DOI: 10.1016/j.clim.2022.109108 -
Trends in Pharmacological Sciences Jan 2023A multicountry outbreak of monkeypox has gained global attention. Basic research including structural and immunological investigation on monkeypox virus (MPXV) is...
A multicountry outbreak of monkeypox has gained global attention. Basic research including structural and immunological investigation on monkeypox virus (MPXV) is central to design effective solutions of treatment with antivirals and appropriate vaccines. We summarize some information about this virus and its re-emergence and the current vaccines that are proposed to limit its spread and present some possible avenues for developing new vaccines.
Topics: Humans; Mpox (monkeypox); Monkeypox virus
PubMed: 36563658
DOI: 10.1016/j.tips.2022.10.005 -
Vaccine Dec 2011Monkeypox (MPX) is a virulent orthopoxvirus that is endemic in some regions of Central Africa. MPX incidence has been rising since the cessation of routine smallpox... (Review)
Review
Monkeypox (MPX) is a virulent orthopoxvirus that is endemic in some regions of Central Africa. MPX incidence has been rising since the cessation of routine smallpox immunization. While it causes significant disease, there is limited person-to-person spread, the incidence is still relatively low, and cases are generally restricted to remote areas that are difficult to access. Therefore, initiating vaccine trials or implementing vaccination programs would be challenging. This paper considers the factors that may influence future decisions on whether MPX vaccination should be pursued.
Topics: Africa, Central; Animals; Endemic Diseases; Humans; Incidence; Mpox (monkeypox); Monkeypox virus; Vaccination
PubMed: 22188935
DOI: 10.1016/j.vaccine.2011.09.004 -
Antiviral Research May 2012Investments in the development of new drugs for orthopoxvirus infections have fostered new avenues of research, provided an improved understanding of orthopoxvirus... (Review)
Review
Investments in the development of new drugs for orthopoxvirus infections have fostered new avenues of research, provided an improved understanding of orthopoxvirus biology and yielded new therapies that are currently progressing through clinical trials. These broad-based efforts have also resulted in the identification of new inhibitors of orthopoxvirus replication that target many different stages of viral replication cycle. This review will discuss progress in the development of new anti-poxvirus drugs and the identification of new molecular targets that can be exploited for the development of new inhibitors. The prototype of the orthopoxvirus group is vaccinia virus and its replication cycle will be discussed in detail noting specific viral functions and their associated gene products that have the potential to serve as new targets for drug development. Progress that has been achieved in recent years should yield new drugs for the treatment of these infections and might also reveal new approaches for antiviral drug development with other viruses.
Topics: Animals; Antiviral Agents; Drug Discovery; Humans; Orthopoxvirus; Virus Replication
PubMed: 22406470
DOI: 10.1016/j.antiviral.2012.02.012 -
Frontiers in Immunology 2020Cells express multiple molecules aimed at detecting incoming virus and infection. Recognition of virus infection leads to the production of cytokines, chemokines and... (Review)
Review
Cells express multiple molecules aimed at detecting incoming virus and infection. Recognition of virus infection leads to the production of cytokines, chemokines and restriction factors that limit virus replication and activate an adaptive immune response offering long-term protection. Recognition of cytosolic DNA has become a central immune sensing mechanism involved in infection, autoinflammation, and cancer immunotherapy. Vaccinia virus (VACV) is the prototypic member of the family Poxviridae and the vaccine used to eradicate smallpox. VACV harbors enormous potential as a vaccine vector and several attenuated strains are currently being developed against infectious diseases. In addition, VACV has emerged as a popular oncolytic agent due to its cytotoxic capacity even in hypoxic environments. As a poxvirus, VACV is an unusual virus that replicates its large DNA genome exclusively in the cytoplasm of infected cells. Despite producing large amounts of cytosolic DNA, VACV efficiently suppresses the subsequent innate immune response by deploying an arsenal of proteins with capacity to disable host antiviral signaling, some of which specifically target cytosolic DNA sensing pathways. Some of these strategies are conserved amongst orthopoxviruses, whereas others are seemingly unique to VACV. In this review we provide an overview of the VACV replicative cycle and discuss the recent advances on our understanding of how VACV induces and antagonizes innate immune activation via cytosolic DNA sensing pathways. The implications of these findings in the rational design of vaccines and oncolytics based on VACV are also discussed.
Topics: Animals; Cytosol; DNA, Viral; Humans; Vaccinia virus; Virus Activation
PubMed: 33117352
DOI: 10.3389/fimmu.2020.568412 -
Cell Mar 2024In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly...
In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).
Topics: Animals; Humans; Mice; Macaca fascicularis; Monkeypox virus; Mpox (monkeypox); Smallpox Vaccine; Vaccines, Combined; Vaccinia virus
PubMed: 38366591
DOI: 10.1016/j.cell.2024.01.017