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PubMed1993

Molecular approaches for the treatment of hemorrhagic fever virus infections.

Viruses causing hemorrhagic fevers in man belong to the following virus groups: togavirus (Chikungunya), flavivirus (dengue, yellow fever, Kyasanur Forest disease, Omsk hemorrhagic fever), arenavirus (Argentinian hemorrhagic fever, Bolivian hemorrhagic fever, Lassa fever), filovirus (Ebola, Marburg), phlebovirus (Rift Valley fever), nairovirus (Crimian-Congo hemorrhagic fever) and hantavirus (hemorrhagic fever with renal syndrome, nephropathic epidemia). Hemorrhagic fever virus infections can be approached by different therapeutic strategies: (i) vaccination; (ii) administration of high-titered antibodies; and (iii) treatment with antiviral drugs. Depending on the molecular target of their interaction, antiviral agents could be classified as follows: IMP dehydrogenase inhibitors (i.e., ribavirin and its derivatives); OMP decarboxylase inhibitors (i.e., pyrazofurin); CTP synthetase inhibitors (i.e., cyclopentylcytosine and cyclopentenylcytosine); SAH hydrolase inhibitors (i.e., neplanocin A); polyanionic substances (i.e., sulfated polymers); interferon and immunomodulators.

Antiviral Agents↗
PubMed1996

Investigation of tick-borne viruses as pathogens of humans in South Africa and evidence of Dugbe virus infection in a patient with prolonged thrombocytopenia.

In the course of investigating suspected cases of viral haemorrhagic fever in South Africa patients were encountered who had been bitten by ticks, but who lacked evidence of infection with Crimean-Congo haemorrhagic fever (CCHF) virus or non-viral tick-borne agents. Cattle sera were tested by enzyme-linked immunoassay to determine whether tick-borne viruses other than CCHF occur in the country. The prevalence of antibody in cattle sera was 905/2116 (42.8%) for CCHF virus, 70/1358 (5.2%) for Dugbe, 21/1358 (1.5%) for louping ill, 6/450 (1.3%) for West Nile, 7/1358 (0.5%) for Nairobi sheep disease, 3/625 (0.5%) for Kadam and 2/450 (0.4%) for Chenuda. No reactions were recorded with Hazara, Bahig, Bhanja, Thogoto and Dhori viruses. The CCHF findings confirmed previous observations that the virus is widely prevalent within the distribution range of ticks of the genus Hyalomma, while antibody activity to Dugbe antigen was detected only within the distribution range of the tick Amblyomma hebraeum. Cross-reactivity for the nairoviruses, Hazara, Nairobi sheep disease and Dugbe, was detected in serum samples from 3/72 human patients with confirmed CCHF infection, and serum from 1/162 other patients reacted monospecifically with Dugbe antigen. The latter patient suffered from febrile illness with prolonged thrombocytopenia.

Animals↗
PubMed2006

Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice.

In 129 mice, infection with the nairovirus Dugbe virus (DUGV) was lethal following intracerebral but not intraperitoneal inoculation. Following both routes of inoculation, immunostaining of tissue sections demonstrated virus-positive cells in the brain, indicating that DUGV is neuroinvasive in mice. Many brain areas were affected and neurones were the main cell type infected. Infected cells showed punctate accumulations of viral nucleoprotein in the cytoplasm, indicative of virus replication sites. Immunostaining for activated caspase 3 demonstrated no evidence of apoptosis. The type I interferon (IFN) system plays a significant role in defence against DUGV, as 129 IFN-alpha/beta R(-/-) mice died rapidly following both intraperitoneal and intracerebral inoculations. Studies were undertaken to determine whether the IFN-inducible proteins, protein kinase R (PKR) and MxA, were important for protection; neither PKR nor constitutively expressed human MxA played significant roles.

Animals↗
PubMed1995

[Tick-transmitted arbovirus in Maghreb].

The problem of arbovirus infections in Maghreb has been relatively neglected in the pst in spite of a rich diversity of biotopes, the presence of potential reservoirs and vectors, and their position on the flight path of the Palearctic-african bird migration systems, western branch. Moreover, West Nile virus has been isolated from southern Algeria since 1968. From 1979 to 1989, ticks were collected from wild birds, pigeons, bats, rodents, poultry, camels, wild boars, domestic mammals and man, and assayed for viruses. On the whole, 424 ticks were virologically studied from Morocco, 582 from Algeria and 601 from Tunisia. Four tick-borne arboviruses have been isolated so far: three from Morocco, Soldado (Nairovirus), Essaouria (Orbivirus) and Kala Iris (Orbivirus) from Ornithodoros (A.) maritimus ticks parasitizing marine birds, and one from Tunisia, Tunis (Phlebovirus), from Argas reflexus hermanni infesting domestic pigeons. Soldado virus may infect man working into colonies of gulls for ornithological or entomological purposes and this infection is associated with a self-limited febrile illness and pruritus. In addition, antibody to Essaouira virus was detected in a wild rodent in Morocco. On the contrary it is unlike that Tunis virus may infect man because A. r. hermanni is a strickly ornithophilic tick. However, Uukuniemi group antibody has been previously evidenced in wild rodents in Tunisia. Finally, it is not excluded that other, more pathogenic, arboviruses such as Congo-Crimean haemorrhagic fever might be accidentally introduced in this sensitive geographical area.

Africa, Northern↗
PubMed1998

[Erve and Eyach: two viruses isolated in France, neuropathogenic for man and widely distributed in Western Europe].

Two arboviruses have been isolated from Mayenne, western France, in 1981-1982, during systematic field surveys: Eyach virus, a cultivirus from Ixodes ricinus and I. ventalloi ticks, and Erve virus, a nairovirus from the tissues of white-toothed shrews, Crocidura russula. For many years, these two viruses were considered as "orphan viruses" without pathogenic power for man, since it became evident that they circulate actively in Europe among populations of wild small and large mammals. Moreover, these viruses are able to infect human beings and were responsible for severe neurological disorders. The presently known geographical distribution of these agents includes France, Germany, Netherlands and Czech Republic.

Coltivirus↗
PubMed2004

Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells.

Crimean-Congo hemorrhagic fever virus is the causative agent of a severe disease throughout Africa, Europe, and Asia. Like other members of the genus Nairovirus, the Crimean-Congo hemorrhagic fever virus contains three genomic RNA segments, the small (S), medium (M), and large (L) segments. The S segment encodes the viral nucleocapsid protein (NP), while the M and L segments encode the glycoproteins and the RNA-dependent RNA polymerase, respectively. In this study, the site of expression and assembly of Crimean-Congo hemorrhagic fever virus NP in mammalian cells have been investigated. It was found that the NP is localized in the perinuclear region of infected cells. By using the Semliki forest virus expression system, it was shown that the Crimean-Congo hemorrhagic fever virus NP is targeted to the perinuclear region of cells in the absence of native RNA segments and virally encoded glycoproteins. It was also demonstrated that the Crimean-Congo hemorrhagic fever virus NP was not expressed as a Golgi-membrane associated protein. By using Cytochalasin D, an agent that disrupts actin filaments, it was found that actin filaments are involved in targeting the viral NP to perinuclear regions. We also demonstrated that disruption of actin filaments reduced the assembly of infectious Crimean-Congo hemorrhagic fever virus up to 97%. Furthermore, we showed that the NP of Crimean-Congo hemorrhagic fever virus NP interacts with actin.

Actin Cytoskeleton↗
PubMed1989

Viruslike particles in liver in sporadic non-A, non-B fulminant hepatitis.

In a patient who followed the typical clinical course of fulminant hepatitis attributable to "sporadic" non-A,non-B (NANB) hepatitis and who finally received treatment by orthotopic liver grafting, three, apparently separate, virus-like agents (26, 45, and 80 nm) and cytoplasmic, reticular tubular structures (CTS) were identified in collapsed and regenerating areas of liver using electron microscopy. The 80-nm particles present within vacuoles, together with the finding of intranuclear rods in association with the smaller particles (26 nm), are similar to those found in the nuclei of cells infected with several different arboviruses. The third type of particle, existing as 45-nm spheres and rods, is similar in morphology only to some form of polyoma virus, which, hitherto, has not been reported as affecting the liver. Unlike typical polyoma virus, replication of the virus "cores" (25-26 nm) was extranuclear and appeared to be occurring in vacuoles. Although analysis for serological markers against a representative panel for arboviruses, flaviviruses, phleboviruses, arenavirus, and nairovirus was negative, an insect vector was implicated in the clinical history.

Adult↗
PubMed1981

Studies on Bunyaviridae including Zaliv Terpeniya virus isolated from Ixodes uriae ticks (Acarina: Ixodidae) in Brittany, France.

Three viruses were isolated from ticks parasitizing nesting seabirds on Cape Sizun, Brittany, France, during the spring of 1979: Soldado like virus (Bunyaviridae, Nairovirus genus) from Ornithodoros (Alectorobius) maritimus (Argasidae), Zaliv Terpeniya (ZT) virus (Bunyaviridae, Uukuvirus genus) from Ixodes (Ceratixodes) uriae (Ixodidae) parasitizing chicks of the kittiwake (Rissa tridactyla), and a virus of the Sakhalin group from I. (C.) uriae. Certain virological and ultrastructural properties of ZT virus were studied and the antigenic relationships between th French isolate and other UUK serogroup viruses from I. (C.) uriae were analyzed in the complement fixation and immune diffusion tests. Cape Sizun is notable for the unusual presence of both argasied (Ornithodoros) and ixodid (Ixodes) ticks infesting seabirds in adjacent niches in a single locality, where they are infected by different viruses.

Animals↗
PubMed2004

[Tick-borne human pathogenic microorganisms found in Europe and those considered nonpathogenic. Part I: Ticks and Viruses].

The importance of tick-borne encephalitis (TBE) and Lyme borreliosis-the main European tick-borne diseases-is steadily growing. This fact is due to many different factors including climate changes. However, across Europe many other human pathogenic viruses, bacteria, and parasites are found in ticks. This article gives an overview of tick-borne human pathogenic viruses present in Europe as well as those considered nonpathogenic. It also deals with the various species of vector-competent ticks. Among these ticks, viruses from 6 families encompassing 8 genera and 35 species are found,whereby the families Flaviviridae, Bunyaviridae, and Reoviridae with the genera flavivirus, nairovirus, and orbivirus are the most prevalent. Because of their special importance Omsk hemorrhagic fever, louping-ill disease, tick-borne encephalitis, and Crimean-Congo hemorrhagic fever are discussed in detail. Although West Nile virus is mainly transmitted to man by mosquitoes, it is discussed in detail, because West Nile fever has become a good example for a new and rapidly spreading vector-borne disease in the USA and for a recurrent one in Europe. Secondly, besides the mosquito-bird cycle an interesting tick--bird cycle is emerging. The overview clearly demonstrates that in Europe (particularly in Germany) tick-borne viruses, with the exception of TBE, constitute an extremely ignored research subject. This lack of attention is in contrast to their importance and results in a lack of necessary scientific data.

Adrenal Cortex Hormones↗
PubMed1983

A sero-epidemiological survey for Bunyaviridae and certain other arboviruses in Pakistan.

Complement fixation test reactions to the following viruses were studied in 372 samples (157 rodents, 172 domestic animals, 43 persons) from Pakistan: Bunyaviridae, Phlebovirus: Phlebotomus fever Sicilian (PFS), Phlebotomus fever Naples (PFN), Karimabad (KAR), Salehabad (SAL); Nairovirus: Crimean-Congo haemorrhagic fever (CCHF), Hazara (HAZ), Dera Ghazi Khan (DGK), Dhori (DHO); Uukuvirus: Manawa (MWA); "possible members": Bakau (BAK), Bhanja (BHA). Reoviridae, Orbivirus: Wad Medani (WM). Unclassified: Wanowrie (WAN). Four of these viruses are Phlebotomus-borne (PFS, PFN, KAR, SAL). The other nine ar tick-borne. Antibodies against each virus were detected in sera from rodents. Antibodies against PFS, PFN, KAR, CCHF, DGK, BHA, WM and WAN viruses were detected in sera from domestic animals. Antibodies against PFS, CCHF, DGK, DHO, MWA, BHA, and BHA and WAN viruses were detected in human sera. The presence in Pakistan of KAR, DHO, BHA, and WAN viruses is documented for the first time. Over-all prevalence rates were highest for BHA (12.1%) and WM (10.7%) viruses, followed by DGK, CCHF, PFN and PFS (4.0 to 5.4%) and DHO, KAR, WAN, SAL, MWA, BAK and HAZ (0.3 to 2.1%). Epidemiological factors relating to virus circulation and human disease are discussed.

Adult↗
PubMedDate not supplied

Arbovirus infections and viral haemorrhagic fevers in Uganda: a serological survey in Karamoja district, 1984.

Sera collected in May 1984 from 132 adult residents of Karamoja district, Uganda, were examined by haemagglutination inhibition tests for antibodies against selected arboviruses, namely Chikungunya and Semliki Forest alphaviruses (Togaviridae); dengue type 2, Wesselsbron, West Nile, yellow fever and Zika flaviviruses (Flaviviridae); Bunyamwera, Ilesha and Tahyna bunyaviruses (Bunyaviridae); and Sicilian sandfly fever phlebovirus (Bunyaviridae); and by immunofluorescence tests against certain haemorrhagic fever viruses, Lassa fever arenavirus (Arenaviridae), Ebola-Sudan, Ebola-Zaïre and Marburg filoviruses (Filoviridae), Crimean-Congo haemorrhagic fever nairovirus and Rift Valley fever phlebovirus (Bunyaviridae). Antibodies against Chikungunya virus were the most prevalent (47%), followed by flavivirus antibodies (16%), which were probably due mainly to West Nile virus. No evidence of yellow fever or dengue virus circulation was observed. A few individuals had antibodies against Crimean-Congo haemorrhagic fever, Lassa, Ebola and Marburg viruses, suggesting that these viruses all circulate in the area.

Adult↗
PubMed1986

Persistent infection of Aedes albopictus C6/36 cells by Bunyamwera virus.

Two cell lines persistently infected with Bunyamwera virus have been established from the C6/36 clone of Aedes albopictus cells. The cells express Bunyamwera virus antigens as detected by immunofluorescence and are resistant to superinfection with Bunyamwera virus and other bunyaviruses, but not Dugbe virus (Nairovirus) nor vesicular stomatitis virus. The virus released from the persistently infected cells developed an altered cloudy or "bull's-eye" plaque morphology with increasing passage level, and a greater temperature sensitivity at 39.5 degrees than standard virus. The persistent virus interfered strongly with the replication of standard Bunyamwera virus in normal C6/36 cells and to a much lesser extent in BHK cells. Interference was not noted with other bunyaviruses or vesicular stomatitis virus. The persistent virus from one cell line, C6/36-PI LO, had a slower migrating nucleocapsid protein on polyacrylamide gels. Analysis of the RNA in persistently infected cells or in persistent virus by Northern blot hybridization with cloned cDNA probes showed that the major viral RNA species was the S segment, while the L and M RNA segments were barely detectable. Our results indicate that Bunyamwera virus can readily establish persistent infections in mosquito cells, and that persistence is accompanied by the generation of viruses with variable genetic and phenotypic characteristics.

Aedes↗
PubMed2004

Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV), which is a member of the Nairovirus genus (family Bunyaviridae). CCHF was first recognized during a large outbreak among agricultural workers in the mid-1940s in the Crimean peninsula. The disease now occurs sporadically throughout much of Africa, Asia, and Europe and results in an approximately 30% fatality rate. After a short incubation period, CCHF is characterized by a sudden onset of high fever, chills, severe headache, dizziness, back, and abdominal pains. Additional symptoms can include nausea, vomiting, diarrhea, neuropsychiatric, and cardiovascular changes. In severe cases, hemorrhagic manifestations, ranging from petechiae to large areas of ecchymosis, develop. Numerous genera of ixodid ticks serve both as vector and reservoir for CCHFV; however, ticks in the genus Hyalomma are particularly important to the ecology of this virus. In fact, occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. Therefore, exposure to these ticks represents a major risk factor for contracting disease; however, other important risk factors are known and are discussed in this review. In recent years, major advances in the molecular detection of CCHFV, particularly the use of real-time reverse transcription-polymerase chain reaction (RT-PCR), in clinical and tick samples have allowed for both rapid diagnosis of disease and molecular epidemiology studies. Treatment options for CCHF are limited. Immunotherapy and ribavirin have been tried with varying degrees of success during sporadic outbreaks of disease, but no case-controlled trials have been conducted. Consequently, there is currently no antiviral treatment for CCHF approved by the U.S. Food and Drug Administration (FDA). However, renewed interested in CCHFV, as well as increased knowledge of its basic biology, may lead to improved therapies in the future. This article reviews the history, epidemiology, ecology, clinical features, pathogenesis, diagnosis, and treatment of CCHF. In addition, recent advances in the molecular biology of CCHFV are presented, and issues related to its possible use as a bioterrorism agent are discussed.

Animals↗
PubMed2004

Sequence analysis of L RNA of Lassa virus.

The L RNA of three Lassa virus strains originating from Nigeria, Ghana/Ivory Coast, and Sierra Leone was sequenced and the data subjected to structure predictions and phylogenetic analyses. The L gene products had 2218-2221 residues, diverged by 18% at the amino acid level, and contained several conserved regions. Only one region of 504 residues (positions 1043-1546) could be assigned a function, namely that of an RNA polymerase. Secondary structure predictions suggest that this domain is very similar to RNA-dependent RNA polymerases of known structure encoded by plus-strand RNA viruses, permitting a model to be built. Outside the polymerase region, there is little structural data, except for regions of strong alpha-helical content and probably a coiled-coil domain at the N terminus. No evidence for reassortment or recombination during Lassa virus evolution was found. The secondary structure-assisted alignment of the RNA polymerase region permitted a reliable reconstruction of the phylogeny of all negative-strand RNA viruses, indicating that Arenaviridae are most closely related to Nairoviruses. In conclusion, the data provide a basis for structural and functional characterization of the Lassa virus L protein and reveal new insights into the phylogeny of negative-strand RNA viruses.

Amino Acid Sequence↗
PubMed2004

Sequence determination of the Crimean-Congo hemorrhagic fever virus L segment.

Crimean-Congo hemorrhagic fever (CCHF) virus is highly pathogenic for humans and remains the only Category A virus for which full sequence information is currently unavailable. In this study we completed CCHF genome characterization by determining the L segment sequence using Dugbe and CCHF virus-specific oligonucleotides. Sequence alignments revealed the presence of four previously described conserved regions in all Bunyaviridae polymerases. Interestingly, additional regions containing putative Ovarian Tumor (OTU)-like cysteine protease and helicase domains were identified in the L segments of CCHF and Dugbe viruses, suggesting an autoproteolytic cleavage process for nairovirus L proteins.

Amino Acid Sequence↗
PubMed2004

Crimean-Congo haemorrhagic fever virus: sequence analysis of the small RNA segments from a collection of viruses world wide.

Crimean-Congo haemorrhagic fever virus (CCHFv) is a member of the genus Nairovirus in the family Bunyaviridae. It possesses a tripartite, single stranded RNA genome of negative polarity consisting of large (L), medium (M) and small (S) segments. CCHF virus is enzootic in life stock and wild animals in many parts of the Middle East, Asia and Africa and is also recognised in Southeast Europe. Severe disease, manifest as haemorrhagic fever and high mortality rates (up to 50%), is only recognised in humans. We have determined the complete sequence of the small genomic RNA segment from several strains of CCHF virus from outbreaks in Pakistan 2000, Baghdad 1976 and Uzbekistan 1967. Phylogenetic analysis of three datasets of sequences from the small genomic RNA segment available from a range of strains indicates that they can be divided into seven subtypes. Superimposed on this pattern are links between distant geographic locations, pointing to the existence of a global reservoir of CCHFv. In some cases these links may originate from trade in livestock, and long-distance carriage of virus or infected ticks during bird migration.

Disease Outbreaks↗
PubMed1982

Blisters, pruritus, and fever after bites by the Arabian tick Ornithodoros (Alectorobius) muesebecki.

A biologist was bitten by Ornithodoros (Alectorobius) muesebecki Hoogstraal, an endemic tick parasite of nesting and resting marine birds on islands in eastern Arabia. Irritating bullae developed and for four months he experienced intermittent inflammation and irritation. Two years earlier, after being bitten by the same tick species on a different island, he had experienced only irritation lasting no more than a fortnight. Petroleum-industry labourers on another island were admitted to hospital for about two weeks with bullae at numerous bite sites, intense pruritus, headache, and fever. Zirqu virus (Bunyaviridae, Nairovirus) has been isolated from O. (A.) muesebecki samples from Abu Dhabi. The role of Zirqa virus and/or of salivary toxins in producing irritation and illness, as well as individual sensitivity to the tick and the seasonal dynamics of toxicity or infectivity, should be investigated.

Bites and Stings↗
PubMed1988

Molecular and biochemical studies of the evolution, infection and transmission of insect bunyaviruses.

Members of the Bunyaviridae family of RNA viruses (bunyaviruses, hantaviruses, nairoviruses, phleboviruses and uukuviruses) have been studied at the molecular and genetic level to understand the basis of their evolution and infection in vertebrate and invertebrate (arthropod) hosts. With the exception of the hantaviruses, these viruses infect and are transmitted by a variety of blood-sucking arthropods (mosquitoes, phlebotomines, gnats, ticks, etc.). The viruses are responsible for infection of various vertebrate species, occasionally causing human disease, morbidity and mortality (e.g. Rift Valley fever, Crimean-Congo haemorrhagic fever, Korean haemorrhagic fever). Genetic and molecular analyses of bunyaviruses have established the coding assignments of the three viral RNA species and documented which viral gene products determine host range and virulence. Ecological studies, with molecular techniques, have provided evidence for bunyavirus evolution in nature through genetic drift (involving the accumulation of point mutations) and shift (RNA-segment reassortment).

Animals↗