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Cell Oct 2016Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an...
Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antibody Specificity; Cowpox; Cowpox virus; Cross Reactions; Humans; Leukocytes, Mononuclear; Mpox (monkeypox); Monkeypox virus; Poxviridae Infections; Smallpox; Vaccinia; Vaccinia virus; Variola virus
PubMed: 27768891
DOI: 10.1016/j.cell.2016.09.049 -
Current Opinion in Virology Oct 2022Poxviruses are large double-stranded DNA viruses that encode their own DNA replication, transcription, and mRNA biogenesis machinery, which underlies their ability to... (Review)
Review
Poxviruses are large double-stranded DNA viruses that encode their own DNA replication, transcription, and mRNA biogenesis machinery, which underlies their ability to replicate entirely in the cytoplasm. However, like all other viruses, poxviruses remain dependent on host ribosomes to translate their mRNAs into the viral proteins needed to complete their replication cycle. While earlier studies established a fundamental understanding of how poxviruses wrestle with their hosts for control of translation initiation and elongation factors that guide ribosome recruitment and mRNA decoding, recent work has begun to reveal the extent to which poxviruses directly target the ribosome itself. This review summarizes our current understanding of the regulation of ribosomes and translation in poxvirus infection.
Topics: Humans; Vaccinia virus; Ribosomes; Poxviridae; Poxviridae Infections; RNA, Messenger; Virus Replication
PubMed: 36270183
DOI: 10.1016/j.coviro.2022.101256 -
Revue Scientifique Et Technique... Aug 2015Myxomatosis, a major disease of European rabbits (Oryctolagus cuniculus), is enzootic on several continents. The disease is infectious, virulent and contagious. The... (Review)
Review
Myxomatosis, a major disease of European rabbits (Oryctolagus cuniculus), is enzootic on several continents. The disease is infectious, virulent and contagious. The pathogen is a virus of the family Poxviridae, genus Leporipoxvirus. In its classic form the disease is often fatal, characterised by severe immunosuppression and the appearance of skin pseudotumours (myxomas); it is conducive to effective mechanical transmission by many biting arthropods. Atypical clinical forms, referred to as amyxomatous, of variable severity and with an apparent preference for direct transmission, have recently emerged in Europe. Virus-host interactions have been particularly well studied since the voluntary introduction of the myxoma virus into Australia and Europe, revealing a remarkable process of co-evolution. Molecular analysis has recently demonstrated the extraordinary evolutionary capacity of the myxoma virus.
Topics: Animals; Myxoma virus; Poxviridae Infections; Rabbits; Tumor Virus Infections
PubMed: 26601455
DOI: No ID Found -
Microbiological Reviews Mar 1991Poxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among... (Review)
Review
Poxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among animal viruses in several respects. First, owing to the cytoplasmic site of virus replication, the virus encodes many enzymes required either for macromolecular precursor pool regulation or for biosynthetic processes. Second, these viruses have a very complex morphogenesis, which involves the de novo synthesis of virus-specific membranes and inclusion bodies. Third, and perhaps most surprising of all, the genomes of these viruses encode many proteins which interact with host processes at both the cellular and systemic levels. For example, a viral homolog of epidermal growth factor is active in vaccinia virus infections of cultured cells, rabbits, and mice. At least five virus proteins with homology to the serine protease inhibitor family have been identified and one, a 38-kDa protein encoded by cowpox virus, is thought to block a host pathway for generating a chemotactic substance. Finally, a protein which has homology with complement components interferes with the activation of the classical complement pathway. Poxviruses infect their hosts by all possible routes: through the skin by mechanical means (e.g., molluscum contagiosum infections of humans), via the respiratory tract (e.g., variola virus infections of humans), or by the oral route (e.g., ectromelia virus infection of the mouse). Poxvirus infections, in general, are acute, with no strong evidence for latent, persistent, or chronic infections. They can be localized or systemic. Ectromelia virus infection of the laboratory mouse can be systemic but inapparent with no mortality and little morbidity, or highly lethal with death in 10 days. On the other hand, molluscum contagiosum virus replicates only in the stratum spinosum of the human epidermis, with little or no involvement of the dermis, and does not spread systemically from the site of infection. The host response to infection is progressive and multifactorial. Early in the infection process, interferons, the alternative pathway of complement activation, inflammatory cells, and natural killer cells may contribute to slowing the spread of the infection. The cell-mediated response involving learned cytotoxic T lymphocytes and delayed-type hypersensitivity components appears to be the most important in recovery from infection. A significant role for specific antiviral antibody and antibody-dependent cell-mediated cytotoxicity has yet to be demonstrated in recovery from a primary infection, but these responses are thought to be important in preventing reinfection.
Topics: Amino Acid Sequence; Animals; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Molecular Sequence Data; Peptides; Poxviridae; Poxviridae Infections; Serpins; Virus Replication
PubMed: 1851533
DOI: 10.1128/mr.55.1.80-122.1991 -
Bulletin of the World Health... 1972Between October 1970 and May 1971, six cases of human infection with monkeypox virus were identified in Liberia, Nigeria, and Sierra Leone. Four of the cases were...
Between October 1970 and May 1971, six cases of human infection with monkeypox virus were identified in Liberia, Nigeria, and Sierra Leone. Four of the cases were confirmed by virus isolation and two were diagnosed on the basis of epidemiological and serological investigations. All the cases occurred in unvaccinated individuals.Post-infection serological studies showed high haemagglutination-inhibition and neutralizing titres to pox group virus in four of the cases. Repeated challenge vaccination of all cases with potent smallpox vaccine resulted in equivocal reactions.In all, 24 susceptible household contacts were exposed to the infected cases, but none developed disease. All the contacts subsequently responded to vaccination with a primary reaction, thus confirming their susceptibility and ruling out asymptomatic infection.
Topics: Adult; Antibodies; Child; Child, Preschool; Female; Hemagglutination Inhibition Tests; Humans; Liberia; Male; Neutralization Tests; Nigeria; Poxviridae; Poxviridae Infections; Sierra Leone
PubMed: 4340216
DOI: No ID Found -
Cell Death and Differentiation Jan 2019The primary function of the immune system is to protect the host from invading pathogens. In response, microbial pathogens have developed various strategies to evade... (Review)
Review
The primary function of the immune system is to protect the host from invading pathogens. In response, microbial pathogens have developed various strategies to evade detection and destruction by the immune system. This tug-of-war between the host and the pathogen is a powerful force that shapes organismal evolution. Regulated cell death (RCD) is a host response that limits the reservoir for intracellular pathogens such as viruses. Since pathogen-specific T cell and B cell responses typically take several days and is therefore slow-developing, RCD of infected cells during the first few days of the infection is critical for organismal survival. This innate immune response not only restricts viral replication, but also serves to promote anti-viral inflammation through cell death-associated release of damage-associated molecular patterns (DAMPs). In recent years, necroptosis has been recognized as an important response against many viruses. The central adaptor for necroptosis, RIPK3, also exerts anti-viral effects through cell death-independent activities such as promoting cytokine gene expression. Here, we will discuss recent advances on how viruses counteract this host defense mechanism and the effect of necroptosis on the anti-viral inflammatory reaction.
Topics: Cytokines; Herpesviridae Infections; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammation; Necroptosis; Poxviridae Infections; RNA Virus Infections; Receptor-Interacting Protein Serine-Threonine Kinases; Virus Diseases; Virus Replication; Viruses
PubMed: 30050058
DOI: 10.1038/s41418-018-0172-x -
Annales de Dermatologie Et de... May 2019Poxvirus (PXV) infections are a common cause of cutaneous signs. In France, certain forms of poxvirus are frequent and benign (molluscum contagiosum), while others are... (Review)
Review
Poxvirus (PXV) infections are a common cause of cutaneous signs. In France, certain forms of poxvirus are frequent and benign (molluscum contagiosum), while others are rare but potentially serious (cowpox virus [CPXV]). Whereas only smallpox and molluscum contagiosum viruses have a human reservoir and are transmitted between humans, most poxvirus infections are zoonoses having only animal reservoirs. Only a small number of poxviruses are responsible for infection in humans, but the increasing number of new pets, some of which are exotic, coupled with the rapid rise in international travel are creating a greater risk of transmission of zoonotic PXV to new vectors and of spread of these diseases to new regions throughout the world. In France, molluscum contagiosum, orf and milkers' nodule give rise to numerous consultations and are well known to dermatologists. However, dermatologists must also be able to identify other parapoxviruses of similar presentation to orf; thus, CPXV and monkeypox are considered potentially emergent viruses with a high risk of epidemic and spread due to increasing international transport and the loss of the maximum protection against smallpox. Finally, despite its declared eradication, smallpox is currently being monitored because of the potential risk of reintroduction, whether accidentally or deliberately through bioterrorism.
Topics: Animals; Communicable Diseases, Emerging; Cowpox; Diagnosis, Differential; Disease Reservoirs; France; Humans; Molluscum Contagiosum; Pets; Poxviridae Infections; Skin Diseases, Viral; Smallpox; Zoonoses
PubMed: 31079914
DOI: 10.1016/j.annder.2019.03.001 -
Veterinary Microbiology Jan 2010Poxviruses compromise a group of long known important pathogens including some zoonotic members affecting lifestock animals and humans. While whole genome sequence... (Review)
Review
Poxviruses compromise a group of long known important pathogens including some zoonotic members affecting lifestock animals and humans. While whole genome sequence analysis started to shed light into the molecular mechanisms underlying host cell infection, viral replication as well as virulence, our understanding of poxvirus maintenance in nature and their transmission to humans is still poor. During the last two decades, reports on emerging human monkeypox outbreaks in Africa and North America, the increasing number of cowpox virus infections in cats, exotic animals and humans and cases of vaccinia virus infections in humans in South America and India reminded us that - beside the eradicated smallpox virus - there are other poxviruses that can cause harm to men. We start to learn that the host range of some poxviruses is way broader than initially thought and that mainly rodents seem to function as virus reservoir. The following review is aiming to provide an up-to-date overview on the epidemiology of zoonotic poxviruses, emphasizing orthopoxviruses. By outlining the current knowledge of poxvirus transmission, we hope to raise the awareness about modes of acquisition of infections and their proper diagnosis.
Topics: Africa; Americas; Animals; Animals, Wild; Cats; Disease Reservoirs; Humans; India; Poxviridae; Poxviridae Infections; Rodentia; Zoonoses
PubMed: 19828265
DOI: 10.1016/j.vetmic.2009.08.026 -
Wiley Interdisciplinary Reviews. RNA Mar 2019Poxviruses are an unusual family of large double-stranded (ds) DNA viruses that exhibit an incredible degree of self-sufficiency and complexity in their replication and... (Review)
Review
Poxviruses are an unusual family of large double-stranded (ds) DNA viruses that exhibit an incredible degree of self-sufficiency and complexity in their replication and immune evasion strategies. Indeed, amongst their approximately 200 open reading frames (ORFs), poxviruses encode approximately 100 immunomodulatory proteins to counter host responses along with complete DNA synthesis, transcription, mRNA processing and cytoplasmic redox systems that enable them to replicate exclusively in the cytoplasm of infected cells. However, like all other viruses poxviruses do not encode ribosomes and therefore remain completely dependent on gaining access to the host translational machinery in order to synthesize viral proteins. Early studies of these intriguing viruses helped discover the mRNA cap and polyadenylated (polyA) tail that we now know to be present on most eukaryotic messages and which play fundamental roles in mRNA translation, while more recent studies have begun to reveal the remarkable lengths poxviruses go to in order to control both host and viral protein synthesis. Here, we discuss some of the central strategies used by poxviruses and the broader battle that ensues with the host cell to control the translation system, the outcome of which ultimately dictates the fate of infection. This article is categorized under: Translation > Translation Regulation.
Topics: Gene Expression Regulation, Viral; Host-Pathogen Interactions; Poxviridae; Poxviridae Infections; Protein Biosynthesis; Viral Proteins
PubMed: 30381906
DOI: 10.1002/wrna.1515 -
British Medical Journal Jan 1973
Topics: Adult; Africa; Animals; Child; Diagnosis, Differential; Humans; Infant; Monkey Diseases; Poxviridae Infections; Smallpox; Zoonoses
PubMed: 4345907
DOI: No ID Found