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PLoS Pathogens Oct 2018
Topics: Biohazard Release; Dual Use Research; Humans; Orthopoxvirus; Poxviridae Infections
PubMed: 30286197
DOI: 10.1371/journal.ppat.1007344 -
Journal of Neurology Jan 2023Cases of monkeypox (MPV) are sharply rising around the world. While most efforts are being focused on the management of the first symptoms of monkeypox, such as... (Review)
Review
Cases of monkeypox (MPV) are sharply rising around the world. While most efforts are being focused on the management of the first symptoms of monkeypox, such as cutaneous lesions and flu-like symptoms, the effect of the monkeypox virus (MPXV) on multiple organs still remains unclear. Recently, several neurological manifestations, such as headache, myalgia, malaise, fatigue, altered consciousness, agitation, anorexia, nausea, and vomiting, have been reported in patients with MPV. In addition, data from experimental studies have indicated that MPXV can gain access to the central nervous system (CNS) through the olfactory epithelium and infected circulatory monocytes/macrophages as two probable neuroinvasive mechanisms. Therefore, there are growing concerns about the long-term effect of MPXV on the CNS and subsequent neurological complications. This paper highlights the importance of the neuroinvasive potential of MPXV, coupled with neurological manifestations.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Nervous System Diseases
PubMed: 35989372
DOI: 10.1007/s00415-022-11339-w -
BMC Medicine May 2023The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may...
BACKGROUND
The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may profoundly impact the transmission of monkeypox virus (MPXV), however the current-day prevalence of antibodies against MPXV among gay men is not well characterized.
METHODS
A cohort of gay men (n = 326) and a cohort of the general adult population (n = 295) were enrolled in this study. Binding antibodies responses against MPXV/vaccinia and neutralizing antibody responses against vaccinia virus (Tiantan strain) were measured. The antibody responses of these two cohorts were then compared, as well as the responses of individuals born before and in/after 1981 (when the smallpox vaccination ceased in China). Finally, the correlation between the anti-MPXV antibody responses and the anti-vaccinia antibody responses, and the associations between preexisting anti-orthopoxvirus antibody responses and the diagnosed sexually transmitted infections (STIs) in the MSM cohort were analyzed separately.
RESULTS
Our data showed that binding antibodies against MPXV H3, A29, A35, E8, B6, M1 proteins and vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the prevalence of anti-vaccinia binding antibodies was significantly higher among individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the positive rates of binding antibody responses against MPXV H3, A29, A35, E8 and M1 proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the positive rates of anti-MPXV B6 and anti-vaccinia neutralizing antibody responses were significantly higher among these individuals compared to those of age-matched participants in the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-MPXV antibody responses were associated with the anti-vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. The positive rates of both the binding and the neutralizing antibody responses were comparable between individuals with and without diagnosed STIs in the MSM cohort.
CONCLUSIONS
Anti-MPXV and anti-vaccinia antibodies could be readily detected in an MSM cohort and a general population cohort. And a higher level of anti-vaccinia neutralizing antibody responses was observed among individuals who did not get vaccinated against smallpox in the MSM cohort compared to age-matched individuals in the general population cohort.
Topics: Male; Humans; Adult; Orthopoxvirus; Antibodies, Neutralizing; Homosexuality, Male; Smallpox; Sexual and Gender Minorities; Mpox (monkeypox); Monkeypox virus; Vaccinia virus; Communicable Diseases; Antibodies, Viral
PubMed: 37189197
DOI: 10.1186/s12916-023-02872-0 -
MSphere Apr 2023The ongoing worldwide monkeypox outbreak is caused by viral lineages (globally referred to as hMPXV1) that are related to but distinct from clade IIb MPXV viruses...
The ongoing worldwide monkeypox outbreak is caused by viral lineages (globally referred to as hMPXV1) that are related to but distinct from clade IIb MPXV viruses transmitted within Nigeria. Analysis of the genetic differences has indicated that APOBEC-mediated editing might be responsible for the unexpectedly high number of mutations observed in hMPXV1 genomes. Here, using 1,624 publicly available hMPXV1 sequences, we analyzed the mutations that accrued between 2017 and the emergence of the current predominant variant (B.1), as well as those that that have been accumulating during the 2022 outbreak. We confirmed an overwhelming prevalence of C-to-T and G-to-A mutations, with a sequence context (5'-TC-3') consistent with the preferences of several human APOBEC3 enzymes. We also found that mutations preferentially occur in highly expressed viral genes, although no transcriptional asymmetry was observed. A comparison of the mutation spectrum and context was also performed against the human-specific variola virus (VARV) and the zoonotic cowpox virus (CPXV), as well as fowlpox virus (FWPV). The results indicated that in VARV genomes, C-to-T and G-to-A changes were more common than the opposite substitutions, although the effect was less marked than for hMPXV1. Conversely, no preference toward C-to-T and G-to-A changes was observed in CPXV and FWPV. Consistently, the sequence context of C-to-T changes confirmed a preference for a T in the -1 position for VARV, but not for CPXV or FWPV. Overall, our results strongly support the view that, irrespective of the transmission route, orthopoxviruses infecting humans are edited by the host APOBEC3 enzymes. Analysis of the viral lineages responsible for the 2022 monkeypox outbreak suggested that APOBEC enzymes are driving hMPXV1 evolution. Using 1,624 public sequences, we analyzed the mutations that accumulated between 2017 and the emergence of the predominant variant and those that characterize the last outbreak. We found that the mutation spectrum of hMPXV1 has been dominated by TC-to-TT and GA-to-AA changes, consistent with the editing activity of human APOBEC3 proteins. We also found that mutations preferentially affect highly expressed viral genes, possibly because transcription exposes single-stranded DNA (ssDNA), a target of APOBEC3 editing. Notably, analysis of the human-specific variola virus (VARV) and the zoonotic cowpox virus (CPXV) indicated that in VARV genomes, TC-to-TT and GA-to-AA changes are likewise extremely frequent. Conversely, no preference toward TC-to-TT and GA-to-AA changes is observed in CPXV. These results suggest that APOBEC3 proteins have an impact on the evolution of different human-infecting orthopoxviruses.
Topics: Animals; Humans; Orthopoxvirus; Mpox (monkeypox); Cowpox virus; Variola virus; Smallpox; Mutation; APOBEC Deaminases
PubMed: 36920219
DOI: 10.1128/msphere.00062-23 -
The Journal of Infection Dec 2022
Topics: Humans; Monkeypox virus; Orthopoxvirus; Antibodies, Monoclonal; Communicable Diseases; Polymerase Chain Reaction
PubMed: 36334727
DOI: 10.1016/j.jinf.2022.10.036 -
Viruses Dec 2017Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are... (Review)
Review
Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses.
Topics: Animals; Antiviral Agents; Communicable Disease Control; France; Humans; Orthopoxvirus; Poxviridae; Poxviridae Infections; Research; Smallpox Vaccine; Viral Proteins
PubMed: 29295488
DOI: 10.3390/v10010003 -
Emerging Infectious Diseases Sep 2018We report detection and full-genome characterization of a novel orthopoxvirus (OPXV) responsible for a fatal infection in a cat. The virus induced skin lesions...
We report detection and full-genome characterization of a novel orthopoxvirus (OPXV) responsible for a fatal infection in a cat. The virus induced skin lesions histologically characterized by leukocyte infiltration and eosinophilic cytoplasmic inclusions. Different PCR approaches were unable to assign the virus to a defined OPXV species. Large amounts of typical brick-shaped virions, morphologically related to OPXV, were observed by electron microscopy. This OPXV strain (Italy_09/17) was isolated on cell cultures and embryonated eggs. Phylogenetic analysis of 9 concatenated genes showed that this virus was distantly related to cowpox virus, more closely related to to ectromelia virus, and belonged to the same cluster of an OPXV recently isolated from captive macaques in Italy. Extensive epidemiologic surveillance in cats and rodents will assess whether cats are incidental hosts and rodents are the main reservoir of the virus. The zoonotic potential of this novel virus also deserves further investigation.
Topics: Animals; Cat Diseases; Cats; Diagnosis, Differential; Fatal Outcome; Italy; Male; Orthopoxvirus; Poxviridae Infections
PubMed: 30124195
DOI: 10.3201/eid2409.171283 -
Archives of Pathology & Laboratory... Jul 2023Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox)...
CONTEXT.—
Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox) virus is now the most pathogenic member of the Orthopoxvirus genus infecting humans. The 2022 global mpox outbreak has focused attention on its potential effects during pregnancy.
OBJECTIVE.—
To understand the comparative effects of different poxvirus infections on pregnancy, including mpox virus, variola virus, vaccinia virus, and cowpox virus. The impact on the pregnant individual, fetus, and placenta will be examined, with particular attention to the occurrence of intrauterine vertical transmission and congenital infection.
DATA SOURCES.—
The data are obtained from the authors' cases and from various published sources, including early historical information and contemporary publications.
CONCLUSIONS.—
Smallpox caused maternal and perinatal death, with numerous cases reported of intrauterine transmission. In endemic African countries, mpox has also affected pregnant individuals, with up to a 75% perinatal case fatality rate. Since the start of the 2022 mpox outbreak, increasing numbers of pregnant women have been infected with the virus. A detailed description is given of the congenital mpox syndrome in a stillborn fetus, resulting from maternal-fetal transmission and placental infection, and the potential mechanisms of intrauterine infection are discussed. Other poxviruses, notably vaccinia virus and, in 1 case, cowpox virus, can also cause perinatal infection. Based on the historical evidence of poxvirus infections, mpox remains a threat to the pregnant population, and it can be expected that additional cases will occur in the future.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Monkeypox virus; Mpox (monkeypox); Placenta; Orthopoxvirus; Variola virus; Poxviridae Infections; Vaccinia virus
PubMed: 36857117
DOI: 10.5858/arpa.2022-0520-SA -
Viruses Jan 2019Orthopoxviruses (OPV) are emerging zoonotic pathogens, and an increasing number of human infections is currently reported in Europe and in other continents, warranting...
Orthopoxviruses (OPV) are emerging zoonotic pathogens, and an increasing number of human infections is currently reported in Europe and in other continents, warranting heightened attention on this topic. Following two OPV infections reported in veterinarians scratched by sick cats in 2005 and 2007 in North-Eastern-Italy, involving a previously undescribed OPV, a similar strain was isolated by a sick cat from the same territory in 2011, i.e., 6 years later, raising attention on OPV circulation in this region. A surveillance program was launched to assess the OPV seroprevalence among the veterinarians working in local veterinary clinics and in the local wild and domestic cat population; seroprevalence was 33.3% in veterinarians and 19.5% in cats. Seroprevalence in cats was unevenly distributed, peaking at 40% in the area where OPV-infected cats had been observed.
Topics: Adult; Animals; Animals, Wild; Antibodies, Viral; Cat Diseases; Cats; Epidemiological Monitoring; Female; Humans; Italy; Male; Middle Aged; Orthopoxvirus; Pets; Poxviridae Infections; Seroepidemiologic Studies; Veterinarians
PubMed: 30691058
DOI: 10.3390/v11020101 -
MMWR. Morbidity and Mortality Weekly... Sep 2022Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and...
Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.
Topics: Animals; Child; Communicable Diseases; Female; Homosexuality, Male; Humans; Male; Mpox (monkeypox); Monkeypox virus; Orthopoxvirus; Sexual and Gender Minorities; Travel; United States
PubMed: 36074752
DOI: 10.15585/mmwr.mm7136e1