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PubMed2003

Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections.

We assessed the activities of 24 different antiviral compounds against smallpox (two strains of variola major and one of variola minor), monkeypox, vaccinia and cowpox viruses by a neutral red uptake assay. To establish assay parameters, we examined viral replication and its inhibition at various times postinfection and at several multiplicities of infection. Drugs were selected to target a range of functions involved in viral replication. Eight compounds (cidofovir, cyclic HPMPC (cHPMPC), HPMPA, ribavirin, tiazofurin, carbocyclic 3-deazaadenosine, 3-deazaneplanocin A and DFBA (1-(2,4-difluorobenzyloxy)adenosine perchlorate)-a derivative of adenosine N1-oxide) inhibited the replication of all three variola strains and the other orthopoxviruses at drug concentrations within a pharmacologically achievable range. Two others (methisazone and bis-POM-PMEA) showed a lesser degree of antiviral effect, while the remainder were inactive. To examine possible naturally occurring drug resistance among a large number of variola isolates obtained from different geographical regions and at different times, we examined the sensitivity of 35 different strains of variola as well as other orthopoxviruses to a subset of three of the most active compounds: cidofovir, cHPMPC, and ribavirin. Preliminary data indicate that nearly all isolates appear to have similar drug sensitivities. These findings are currently being verified and expanded.

Animals↗
PubMed2003

A case of severe monkeypox virus disease in an American child: emerging infections and changing professional values.

Monkeypox virus disease is a rare zoonosis that until recently was limited to Central Africa. We describe the clinical features of the third child in the United States reported with this newly emerging infection. This child was part of a large cluster of individuals in the Midwest infected by prairie dogs that had contracted the virus when housed with infected small mammals imported from Africa. The differential and laboratory diagnoses and the difficulty finding physicians and nurses to care for this patient are discussed.

Child↗
PubMed1984

Monoclonal antibodies to a monkeypox virus polypeptide determinant.

Three monkeypox virus (MPV) antibody-secreting murine monoclones were characterized as being of the immunoglobulin G1 isotype, gave a 4+ reaction in the indirect fluorescent-antibody test, gave a positive reaction in the enzyme immunoassay, and did not neutralize MPV. These monoclonal antibodies were determined by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis transblot method to react to a 15,500-molecular-weight MPV polypeptide. This reactivity could not be removed by adsorption to a vaccinia virus-infected cell suspension. The three monoclonal antibodies were specific for MPV when tested against epidemiologically unrelated isolates of cowpox virus, variola virus, vaccinia virus, and MPV.

Animals↗
PubMed1979

Monkeypox virus as a source of whitepox viruses.

Monkeypox virus cloning and isolation of the so-called 'white' clones from white pocks which this virus forms on the chorioallantoic membrane (CAM) were carried out. The isolated clones were stable and differed considerably from the parental strain. By their properties, they were identical to whitepox viruses formerly isolated from wildlife monkeys and rodents in Equatorial Africa. Besides stable 'white' clones, a number of virus cultures in the process of cloning were obtained which differed in quantitative content of virions, forming on CAM white pocks and pocks with hemorrhages. It appeared that the properties of the viral population as a whole (reaction type on rabbit skin, hemagglutination activity, etc.) depended on the rate of virions produced with different characteristics.

Animals↗
PubMed2003

Multistate outbreak of monkeypox--Illinois, Indiana, and Wisconsin, 2003.

CDC has received reports of patients with a febrile rash illness who had close contact with pet prairie dogs and other animals. The Marshfield Clinic, Marshfield, Wisconsin, identified a virus morphologically consistent with a poxvirus by electron microscopy of skin lesion tissue from a patient, lymph node tissue from the patient's pet prairie dog, and isolates of virus from culture of these tissues. Additional laboratory testing at CDC indicated that the causative agent is a monkeypox virus, a member of the orthopoxvirus group. This report summarizes initial descriptive epidemiologic, clinical, and laboratory data, interim infection-control guidance, and new animal import regulations.

Adolescent↗
PubMedDate not supplied

[Comparative study of variola virus and monkeypox virus interferon-gamma-binding].

DNA fragments containing genes for coding IFN-gamma-binding proteins (IFNgammaBPs) of variola virus (VARV) and monkeypox virus (MPXV) were obtained from viral genomes using PCR. Isolated genes coding desired proteins were expressed in the insect Sf21 cells using baculovirus expression system. Secreted recombinant IFNgammaBPs were isolated from culture medium of infected Sf21 cells through affinity chromatography procedure. SDS-PAAG and Western blot analysis of culture medium of infected insect cells and preparations of purified recombinant IFNgammaBPs indicated that recombinant viral proteins were dimerized even in the absence of ligand (hIFNgamma) unlike their cell (eucaryotic) analogs. Biological activity of the recombinant IFNgammaBPs were studied in the test of protective effect inhibition of hIFNgamma on L68 cells infected with murine encephalomyocarditis virus. It was shown that recombinant IFNgammaBPs had dose-dependent IFNgamma-inhibiting activity. A possibility of the elaboration of new therapeutics for anti-hIFNgamma therapy on the base of IFNgammaBPs is discussed.

Amino Acid Sequence↗
PubMed1991

[Variola or a severe case of varicella? A case of human variola due to monkeypox virus in a child from the Cameroon].

Human monkeypox was suspected on clinical grounds in a seven years old child in Cameroon. The diagnosis was confirmed at the Center for Disease Control (CDC) in Atlanta, USA. This condition is rare. The present case is the third in Cameroon. An epidemiological and clinical survey carried out in the family and in the area where the patient lives, did not allow to identify other cases. The clinical evolution of the case was good as in those described elsewhere.

Cameroon↗
PubMed1976

Monkeypox and whitepox viruses in West and Central Africa.

Prospects for the eradication of smallpox are now highly encouraging. With the cessation of man-to-man transmission, the question of possible animal reservoirs of smallpox becomes increasingly important. During the period 1970-1975, 20 cases of a smallpox-like disease were detected in smallpox-free areas of tropical rain forest in West and Central Africa. Epidemiological and virological investigations revealed that the disease was caused by an animal poxvirus termed monkeypox virus, a member of the orthopox virus group. The disease spread with difficulty even among susceptible close contacts and does not appear to be sufficiently transmissible to permit continuing infection to become established in man. During the investigations, four orthopox viruses termed whitepox viruses were isolated from rodents and monkeys. The isolates were not distinguishable from variola virus with currently available laboratory techniques, but there is no evidence so far that viruses of this group have infected man. Although there is now substantial and accumulating evidence that there is no animal reservoir for smallpox, continued surveillance and studies in West and Central Africa are warranted.

Africa, Central↗
PubMed1977

Differentiation of variola, monkeypox, and vaccinia antisera by radioimmunoassay.

Poxvirus antisera adsorbed with "homologous" and "heterologous" poxvirus-infected chorioallantoic membranes (CAM) were differentiated by solid-phase radioimmunoassay (RIA). Mixtures of the antiserum dilutions and infected CAM were added directly (without centrifugation) to poxvirus-infected CAM antigens affixed to wells of microtitration plates. The affixed antigens combined with unadsorbed antibodies, and the cross-reactive antigen-antibody complexes were removed by washing. The results showed that adsorption of an antiserum with variola-, vaccinia-, or uninfected-CAM antigen and subsequent reaction of each in RIA with monkeypox- and uninfected-CAM antigens allowed the identification of antivariola, antivaccinia, or antimonkeypox sera.

Antigens, Viral↗
PubMed1988

Clinico-epidemiological features of monkeypox patients with an animal or human source of infection.

Clinical and laboratory examinations were carried out on a total of 338 monkeypox patients in Zaire from 1981 to 1986. An animal source of infection was suspected in 245 (72%) and interhuman transmission for the remaining 93 patients. Among those whose infection was presumably acquired from an animal source, the most affected groups were children aged 3-4 years (27%) and 5-6 years (20%), while only 4% of cases were over 15 years old; there was a considerable preponderance of males (58%) over females (42%), especially in the age group 5-14 years. Among those presumably infected by person-to-person transmission, the age distribution was more uniform, adult patients tending to be relatively more common, and there were more females (57%) than males (43%).Based on comparisons of the frequency and intensity of clinical signs and symptoms among patients infected from an animal source and those who were infected by another patient, there was no evidence that the disease becomes more severe and the transmitted virus more virulent or more easily transmissible from person to person after one or more passages through human hosts.

Adolescent↗
PubMed1987

Monkeypox virus in relation to the ecological features surrounding human settlements in Bumba zone, Zaire.

Since monkeypox virus was discovered in animals in 1958 and in man in 1971, several efforts have been made to identify the reservoir of the virus in nature. In July 1985 a study on human environments and animals suspected to maintain virus transmission was carried out in northern Zaire. The study revealed three well demarcated areas: the human settlement area, the agricultural area and the primary tropical rain forest. The first two were found inhabited by terrestrial and arboreal rodents and bats, while the larger animals have abandoned them. Data on human morbidity collected in the preceding years suggested that most of the patients were infected either in the settlement or in the agricultural area. Isolation of the virus from a squirrel confirmed this suggestion and proved, on the other hand, that the virus could circulate in an area deprived of the larger wild animals, including primates. The virus isolation and results of serologic testing suggest that out of three groups of animals inhabiting the agricultural area, the squirrels Funisciurus anerythrus should be considered a priority candidate to sustain virus transmission.

Adolescent↗
PubMedDate not supplied

[Monkeypox: second human case observed in Ivory Coast (rural health sector of Daloa].

A second case of human monkeypox (world fifty-forth case) has been observed in Ivory Coast (rural health sector of Daloa). A three years old girl presented a major pox-like eruption which evolved to recovery. The authors describe the eruption, the evolution of the sickness, and the scars observed at the fourth month after recovery. It has not been possible to prove neither animal-human nor interhuman contagion.

Child, Preschool↗
PubMed2003

Practical synthesis of D- and l-2-cyclopentenone and their utility for the synthesis of carbocyclic antiviral nucleosides against orthopox viruses (smallpox, monkeypox, and cowpox virus).

Highly efficient and practical methodology for the syntheses of D- and l-4,5-O-isopropylidene-2-cyclopentenone (9 and 22), versatile intermediates for the synthesis of carbocyclic nucleosides, have been developed via a ring-closing metathesis reaction from d-ribose in eight steps. The utility of D- and l-4,5-O-isopropylidene-2-cyclopentenone is demonstrated by their application for the preparation of D-cyclopentyl-6-azauridine 12 and D-cyclopentenyl-5-halocytosine nucleosides (33-35) using Mitsunobu reaction to introduce pyrimidine bases as potential antiviral agents. Preliminary antiviral activity against orthopox viruses (smallpox, monkeypox, and cowpox virus) of the synthesized nucleosides are described.

Antiviral Agents↗
PubMed2026

Structure and operating principles of a monkeypox virus replisome.

Poxviruses are double-stranded DNA viruses with large genomes. Among them, monkeypox virus (MPXV) has been responsible for two recent public health emergencies as declared by the World Health Organization1. The MPXV polymerase comprises three subunits-a catalytic subunit (F8) and a heterodimeric processivity factor (A22 and E4). The viral polymerase must coordinate activities with the hexameric helicase-primase (E5) to initiate replication of the viral genome2. Although structures of MPXV E5 (refs. 3,4) and the polymerase5-7 in isolation are available, how they assemble into a functional replisome remains unclear. In isolation, E5 is in an autoinhibited conformation and has very weak helicase activity3,4, and the mechanism for helicase activation is unclear. Here we used cryo-electron microscopy to determine the structures of DNA-bound MPXV replisomes comprising the polymerase holoenzyme (F8, A22 and E4) and the E5 helicase hexamer. We show that, during replisome assembly, E5 undergoes large-scale conformational changes that allow two of its primase domains to interact with the polymerase F8 thumb and A22 subunit. Biochemical assays and single-molecule experiments reveal that this E5 conformational change is coupled to helicase activation and enhances primase activity. Taken together, these findings identify fundamental mechanisms governing coordinated helicase and polymerase activities during DNA replication for an important class of viral pathogens.

Journal Article↗
PubMed1997

Human monkeypox in Kasai Oriental, Zaire (1996-1997).

Monkeypox is an orthopoxvirus with enzootic circulation in the rainforests of central and western Africa; the virus can be transmitted to humans and cause a syndrome clinically similar to smallpox (e.g., pustular rash, fever, respiratory symptoms, and in

Journal Article↗
PubMed1972

Human monkeypox.

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.

Adult↗
PubMed2004

Human monkeypox.

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Animals↗