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Pathogens (Basel, Switzerland) Aug 2021Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of... (Review)
Review
Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF-based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules.
PubMed: 34451529
DOI: 10.3390/pathogens10081065 -
Pathogens (Basel, Switzerland) Aug 2021The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the... (Review)
Review
The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the ubiquitin system holds a unique mechanism to provide selectivity and specificity in manipulating protein function. As intracellular parasites viruses have evolved to modulate the cellular environment to facilitate replication and subvert antiviral responses. Poxviruses are a large family of dsDNA viruses with large coding capacity that is used to synthetise proteins and enzymes needed for replication and morphogenesis as well as suppression of host responses. This review summarises our current knowledge on how poxvirus functions rely on the cellular ubiquitin system, and how poxviruses exploit this system to their own advantage, either facilitating uncoating and genome release and replication or rewiring ubiquitin ligases to downregulate critical antiviral factors. Whilst much remains to be known about the intricate interactions established between poxviruses and the host ubiquitin system, our knowledge has revealed crucial viral processes and important restriction factors that open novel avenues for antiviral treatment and provide fundamental insights on the biology of poxviruses and other virus families.
PubMed: 34451498
DOI: 10.3390/pathogens10081034 -
Risk Analysis : An Official Publication... May 2019With the advance of biotechnology, biological information, rather than biological materials, is increasingly the object of principal security concern. We argue that both...
With the advance of biotechnology, biological information, rather than biological materials, is increasingly the object of principal security concern. We argue that both in theory and in practice, existing security approaches in biology are poorly suited to manage hazardous biological information, and use the cases of Mousepox, H5N1 gain of function, and Botulinum toxin H to highlight these ongoing challenges. We suggest that mitigation of these hazards can be improved if one can: (1) anticipate hazard potential before scientific work is performed; (2) consider how much the new information would likely help both good and bad actors; and (3) aim to disclose information in the manner that maximally disadvantages bad actors versus good ones.
Topics: Animals; Biotechnology; Bioterrorism; Botulinum Toxins; Computer Security; Decision Making; Ectromelia, Infectious; Hazardous Substances; Humans; Influenza A Virus, H5N1 Subtype; Influenza, Human; Risk; Safety; Security Measures
PubMed: 30419157
DOI: 10.1111/risa.13235 -
Indian Pediatrics Feb 2004
Topics: Abnormalities, Multiple; Autopsy; Ectromelia; Fatal Outcome; Humans; India; Infant, Newborn; Severity of Illness Index
PubMed: 15004311
DOI: No ID Found -
Viruses Jun 2021Ectromelia virus (ECTV), the causative agent of mousepox, has threatened laboratory mouse colonies worldwide for almost a century. Mousepox has been valuable for the... (Comparative Study)
Comparative Study
Ectromelia virus (ECTV), the causative agent of mousepox, has threatened laboratory mouse colonies worldwide for almost a century. Mousepox has been valuable for the understanding of poxvirus pathogenesis and immune evasion. Here, we have monitored in parallel the pathogenesis of nine ECTVs in BALB/cJ mice and report the full-length genome sequence of eight novel ECTV isolates or strains, including the first ECTV isolated from a field mouse, ECTV-MouKre. This approach allowed us to identify several genes, absent in strains attenuated through serial passages in culture, that may play a role in virulence and a set of putative genes that may be involved in enhancing viral growth in vitro. We identified a putative strong inhibitor of the host inflammatory response in ECTV-MouKre, an isolate that did not cause local foot swelling and developed a moderate virulence. Most of the ECTVs, except ECTV-Hampstead, encode a truncated version of the P4c protein that impairs the recruitment of virions into the A-type inclusion bodies, and our data suggest that P4c may play a role in viral dissemination and transmission. This is the first comprehensive report that sheds light into the phylogenetic and geographic relationship of the worldwide outbreak dynamics for the ECTV species.
Topics: Animals; Disease Models, Animal; Ectromelia virus; Ectromelia, Infectious; Female; Genomics; Immune Evasion; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Phylogeny; Phylogeography; Viral Proteins; Virulence
PubMed: 34203773
DOI: 10.3390/v13061146 -
Journal of Medical Case Reports Apr 2021Sirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000-70,000 pregnancies. Sirenomelia is...
BACKGROUND
Sirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000-70,000 pregnancies. Sirenomelia is mainly characterized by the fusion of lower limbs and is widely associated with severe urogenital and gastrointestinal malformations. The presence of a single umbilical artery derived from the vitelline artery is the main anatomical feature distinguishing sirenomelia from caudal regression syndrome. First-trimester diagnosis of this disorder and induced abortion may be the safest medical option. In this report, two cases of sirenomelia that occurred in an white family will be discussed.
CASE PRESENTATION
We report two white cases of sirenomelia occurring in a 31-year-old multigravid pregnant woman. In the first pregnancy (18 weeks of gestation) abortion was performed, but in the third pregnancy (32 weeks) the stillborn baby was delivered by spontaneous vaginal birth. In the second and fourth pregnancies, however, she gave birth to normal babies. Three-dimensional ultrasound imaging showed fusion of the lower limbs. Neither she nor any member of her family had a history of diabetes. In terms of other risk factors, she had no history of exposure to teratogenic agents during her pregnancy. Also, her marriage was non-consanguineous.
CONCLUSION
This report suggests the existence of a genetic background in this mother with a Mendelian inheritance pattern of 50% second-generation incidence in her offspring.
Topics: Abortion, Induced; Adult; Ectromelia; Female; Humans; Imaging, Three-Dimensional; Pregnancy; Pregnancy Trimester, First; Ultrasonography, Prenatal
PubMed: 33902682
DOI: 10.1186/s13256-021-02699-4 -
PLoS Genetics 2013Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS) are severe developmental maladies that present with nearly an identical suite of multi-spectrum birth... (Review)
Review
Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS) are severe developmental maladies that present with nearly an identical suite of multi-spectrum birth defects. Not surprisingly, RBS and CdLS arise from mutations within a single pathway--here involving cohesion. Sister chromatid tethering reactions that comprise cohesion are required for high fidelity chromosome segregation, but cohesin tethers also regulate gene transcription, promote DNA repair, and impact DNA replication. Currently, RBS is thought to arise from elevated levels of apoptosis, mitotic failure, and limited progenitor cell proliferation, while CdLS is thought to arise, instead, from transcription dysregulation. Here, we review new information that implicates RBS gene mutations in altered transcription profiles. We propose that cohesin-dependent transcription dysregulation may extend to other developmental maladies; the diagnoses of which are complicated through multi-functional proteins that manifest a sliding scale of diverse and severe phenotypes. We further review evidence that cohesinopathies are more common than currently posited.
Topics: Apoptosis; Cell Cycle Proteins; Cell Proliferation; Chromosomal Proteins, Non-Histone; Chromosome Segregation; Craniofacial Abnormalities; De Lange Syndrome; Ectromelia; Humans; Hypertelorism; Metabolic Networks and Pathways; Mutation; Cohesins
PubMed: 24367282
DOI: 10.1371/journal.pgen.1004036 -
BMJ Case Reports Jun 2016Tibial hemimelia (congenital longitudinal deficiency of the tibia) is rare (1 in 1 000 000). There are several classifications in the literature. We report an...
Tibial hemimelia (congenital longitudinal deficiency of the tibia) is rare (1 in 1 000 000). There are several classifications in the literature. We report an unclassified case of tibial hemimelia. A 6-year-old girl presented with shortening of the right lower limb, with a small rudimentary foot (presence of all toes) and hyper lax ankle. Quadriceps function was excellent. Radiograph showed a partial tibia and fibula in synostosis. The Jones and Kalamachi type 2 classifications both mention similar tibial anomalies; however, the fibula is normal in both varieties. The present variety can be considered as a variant of type 2 tibial hemimelia.
Topics: Abnormalities, Multiple; Child; Ectromelia; Female; Fibula; Humans; Leg; Prostheses and Implants; Radiography; Synostosis; Tibia
PubMed: 27277586
DOI: 10.1136/bcr-2016-215305 -
Viruses Dec 2022In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the... (Review)
Review
In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, we propose that chickenpox (human herpesvirus-3 infection) is a risk factor for acquisition of monkeypox infection. Our hypothesis states that the chickenpox skin lesion provides an entry site for the monkeypox virus, which is harbored on a fomite in the environment of the patient. The fact that monkeypox can enter via a scratch or abrasion is a known mechanism of spread for three other poxviruses, including mousepox (ectromelia), orf and molluscum contagiosum. There are many similarities in pathogenesis between certain poxviruses and chickenpox, including a viremia with a cellular stress response leading to high levels of the IL-6 cytokine. One very revealing observation in the two epidemiology studies was that the number of pox as well as the severity of disease in children with chickenpox and monkeypox coinfection was not greater than found in children with monkeypox alone. Based on the above observations, we conclude that, when chickenpox precedes monkeypox, priming of the immune system by the earlier chickenpox infection moderates the severity of the secondary infection with monkeypox. This conclusion also has important public health implications about chickenpox surveillance.
Topics: Adolescent; Young Adult; Humans; Child; Chickenpox; Mpox (monkeypox); Coinfection; Herpesvirus 3, Human; African People
PubMed: 36560805
DOI: 10.3390/v14122800 -
American Journal of Medical Genetics.... Nov 2011Epidemiologic data on phocomelia are scarce. This study presents an epidemiologic analysis of the largest series of phocomelia cases known to date. Data were provided by... (Review)
Review
Phocomelia: a worldwide descriptive epidemiologic study in a large series of cases from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature.
Epidemiologic data on phocomelia are scarce. This study presents an epidemiologic analysis of the largest series of phocomelia cases known to date. Data were provided by 19 birth defect surveillance programs, all members of the International Clearinghouse for Birth Defects Surveillance and Research. Depending on the program, data corresponded to a period from 1968 through 2006. A total of 22,740,933 live births, stillbirths and, for some programs, elective terminations of pregnancy for fetal anomaly (ETOPFA) were monitored. After a detailed review of clinical data, only true phocomelia cases were included. Descriptive data are presented and additional analyses compared isolated cases with those with multiple congenital anomalies (MCA), excluding syndromes. We also briefly compared congenital anomalies associated with nonsyndromic phocomelia with those presented with amelia, another rare severe congenital limb defect. A total of 141 phocomelia cases registered gave an overall total prevalence of 0.62 per 100,000 births (95% confidence interval: 0.52-0.73). Three programs (Australia Victoria, South America ECLAMC, Italy North East) had significantly different prevalence estimates. Most cases (53.2%) had isolated phocomelia, while 9.9% had syndromes. Most nonsyndromic cases were monomelic (55.9%), with an excess of left (64.9%) and upper limb (64.9%) involvement. Most nonsyndromic cases (66.9%) were live births; most isolated cases (57.9%) weighed more than 2,499 g; most MCA (60.7%) weighed less than 2,500 g, and were more likely stillbirths (30.8%) or ETOPFA (15.4%) than isolated cases. The most common associated defects were musculoskeletal, cardiac, and intestinal. Epidemiological differences between phocomelia and amelia highlighted possible differences in their causes.
Topics: Adult; Americas; Australia; Biomedical Research; China; Congenital Abnormalities; Ectromelia; Epidemiologic Studies; Europe; Female; Humans; Infant, Newborn; International Cooperation; Male; Population Surveillance; Pregnancy; Prevalence; Registries; Young Adult
PubMed: 22002800
DOI: 10.1002/ajmg.c.30320