Pestivirus
Diarrhea Viruses, Bovine Viral
Classical swine fever virus
Border disease virus
Diarrhea Virus 1, Bovine Viral
Genetic diversity of pestiviruses: identification of novel groups and implications for classification. (1/25)
The complete Npro coding sequences were determined for 16 pestiviruses isolated from cattle, pig, and several wild ruminant species including reindeer, bison, deer, and bongo. Phylogenetic analysis enabled the segregation of pestiviruses into the established species bovine viral diarrhea virus-1 (BVDV-1), BVDV-2, border disease virus (BDV), and classical swine fever virus (CSFV). For BVDV-1 five distinct subgroups were identified, while BVDV-2, BDV, and CSFV were each subdivided into two subgroups. The virus isolates from bongo and deer as well as one porcine virus isolate belong to BVDV-1. Interestingly, the isolates from reindeer and bison are distinct from the established pestivirus species. The Npro sequences from these two viruses are more similar to BDV than to the other pestivirus species. Calculation of the pairwise evolutionary distances allowed a clear separation of the categories species, subgroup, and isolate only when the reindeer/bison viruses were considered as members of an additional pestivirus species. Furthermore, the entire E2 coding sequences of a representative set of virus isolates covering all recognized species and subgroups were studied. Segregation of pestiviruses based on the E2 region was identical with that obtained with the N(pro) sequences. (+info)Enzyme-linked immunosorbent assay using a virus type-specific peptide based on a subdomain of envelope protein E(rns) for serologic diagnosis of pestivirus infections in swine. (2/25)
Peptides deduced from the C-terminal end (residues 191 to 227) of pestivirus envelope protein E(rns) were used to develop enzyme-linked immunosorbent assays (ELISAs) to measure specifically antibodies against different types of pestiviruses. The choice of the peptide was based on the modular structure of the E(rns) protein, and the peptide was selected for its probable independent folding and good exposure, which would make it a good candidate for an antigenic peptide to be used in a diagnostic test. A solid-phase peptide ELISA which was cross-reactive for several types of pestivirus antibodies and which can be used for the general detection of pestivirus antibodies was developed. To identify type-specific pestivirus antibodies, a liquid-phase peptide ELISA, with a labeled, specific classical swine fever virus (CSFV) peptide and an unlabeled bovine viral diarrhea virus peptide to block cross-reactivity, was developed. Specificity and sensitivity of the liquid-phase peptide ELISA for CSFV were 98 and 100%, respectively. Because the peptide is a fragment of the E(rns) protein, it can be used to differentiate between infected and vaccinated animals when a vaccine based on the E2 protein, which is another pestivirus envelope protein, is used. (+info)A cellular J-domain protein modulates polyprotein processing and cytopathogenicity of a pestivirus. (3/25)
Pestiviruses are positive-strand RNA viruses closely related to human hepatitis C virus. Gene expression of these viruses occurs via translation of a polyprotein, which is further processed by cellular and viral proteases. Here we report the formation of a stable complex between an as-yet-undescribed cellular J-domain protein, a member of the DnaJ-chaperone family, and pestiviral nonstructural protein NS2. Accordingly, we termed the cellular protein Jiv, for J-domain protein interacting with viral protein. Jiv has the potential to induce in trans one specific processing step in the viral polyprotein, namely, cleavage of NS2-3. Efficient generation of its cleavage product NS3 has previously been shown to be obligatory for the cytopathogenicity of the pestiviruses. Regulated expression of Jiv in cells infected with noncytopathogenic bovine viral diarrhea virus disclosed a direct correlation between the intracellular level of Jiv, the extent of NS2-3 cleavage, and pestiviral cytopathogenicity. (+info)The carboxy-terminal sequence of the pestivirus glycoprotein E(rns) represents an unusual type of membrane anchor. (4/25)
The E(rns) protein is a structural glycoprotein of pestiviruses that lacks a typical membrane anchor sequence and is known to be secreted from the infected cell. However, major amounts of the protein are retained within the cell and attached to the virion by a so far unknown mechanism. Transient-expression studies with cDNA constructs showed that in a steady-state situation, 16% of the protein is found in the supernatant of the transfected cells while 84% appears as intracellular protein. We show here that E(rns) represents a membrane-bound protein. Membrane binding occurs via the carboxy-terminal region of E(rns). By fusion of this sequence to the carboxy terminus of green fluorescent protein (GFP), the subcellular localization of the reporter protein switched from cytosolic to membrane bound. A core sequence of 11 amino acids necessary for membrane binding was elicited in truncation experiments with GFP constructs. However, this peptide is not sufficient to confer membrane anchoring but needs either upstream or downstream accessory sequences. Analyses with different extraction procedures showed that E(rns) is neither easily stripped from the membrane, like a peripheral membrane protein, nor as tightly membrane bound as a transmembrane protein. (+info)Bovine viral diarrhea virus: prevention of persistent fetal infection by a combination of two mutations affecting Erns RNase and Npro protease. (5/25)
Different genetically engineered mutants of bovine viral diarrhea virus (BVDV) were analyzed for the ability to establish infection in the fetuses of pregnant heifers. The virus mutants exhibited either a deletion of the overwhelming part of the genomic region coding for the N-terminal protease N(pro), a deletion of codon 349, which abrogates the RNase activity of the structural glycoprotein E(rns), or a combination of both mutations. Two months after infection of pregnant cattle with wild-type virus or either of the single mutants, the majority of the fetuses contained virus or were aborted or found dead in the uterus. In contrast, the double mutant was not recovered from fetal tissues after a similar challenge, and no dead fetuses were found. This result was verified with a nonrelated BVDV containing similar mutations. After intrauterine challenge with wild-type virus, mutated viruses, and cytopathogenic BVDV, all viruses could be detected in fetal tissue after 5, 7, and 14 days. Type 1 interferon (IFN) could be detected in fetal serum after challenge, except with wild-type noncytopathogenic BVDV. On days 7 and 14 after challenge, the largest quantities of IFN in fetal serum were induced by the N(pro) and RNase-negative double mutant virus. The longer duration of fetal infection with the double mutant resulted in abortion. Therefore, for the first time, we have demonstrated the essential role of both N(pro) and E(rns) RNase in blocking interferon induction and establishing persistent infection by a pestivirus in the natural host. (+info)Natural infection of cattle with an atypical 'HoBi'-like pestivirus--implications for BVD control and for the safety of biological products. (6/25)
During a study on Bovine Viral Diarrhoea (BVD) epidemiology in Thailand, a pestivirus was detected in serum from a calf. Comparative nucleotide sequence analysis showed that this virus was closely related to a recently described atypical pestivirus (D32/00_'HoBi') that was first isolated from a batch of foetal calf serum collected in Brazil. The results from virus neutralisation tests performed on sera collected from cattle in the herd of the infected calf, showed that these cattle had markedly higher antibody titres against the atypical pestivirus 'HoBi' than against Bovine Viral Diarrhoea Virus types 1 and 2, or Border Disease Virus. The results also supported, consequently, the results from the molecular analysis, and demonstrated that a 'HoBi'-like pestivirus had been introduced to, and was now circulating in the herd. This study is the first to report a natural infection in cattle with a virus related to this atypical pestivirus, and it suggests that this group of pestiviruses may already be spread in cattle populations. The findings have implications for BVD control and for the biosafety of vaccines and other biological products produced with foetal calf serum. Consequently, these atypical pestiviruses should be included in serological assays, and any diagnostic assay aimed at detection of pestiviruses in biological products or animals should be tested for its ability to detect them. (+info)The imidazopyrrolopyridine analogue AG110 is a novel, highly selective inhibitor of pestiviruses that targets the viral RNA-dependent RNA polymerase at a hot spot for inhibition of viral replication. (7/25)
Ethyl 2-methylimidazo[1,2-a]pyrrolo[2,3-c]pyridin-8-carboxylate (AG110) was identified as a potent inhibitor of pestivirus replication. The 50% effective concentration values for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect, viral RNA synthesis, and production of infectious virus were 1.2 +/- 0.5 microM, 5 +/- 1 microM, and 2.3 +/- 0.3 microM, respectively. AG110 proved inactive against the hepatitis C virus and a flavivirus. AG110 inhibits BVDV replication at a time point that coincides with the onset of intracellular viral RNA synthesis. Drug-resistant mutants carry the E291G mutation in the viral RNA-dependent RNA polymerase (RdRp). AG110-resistant virus is cross-resistant to the cyclic urea compound 1453 which also selects for the E291G drug resistance mutation. Moreover, BVDV that carries the F224S mutation (because of resistance to the imidazopyridine 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine [BPIP]and VP32947) is also resistant to AG110. AG110 did not inhibit the in vitro activity of recombinant BVDV RdRp but inhibited the activity of BVDV replication complexes (RCs). Molecular modeling revealed that E291 is located in a small cavity near the tip of the finger domain of the RdRp about 7 A away from F224. Docking of AG110 in the crystal structure of the BVDV RdRp revealed several potential contacts including with Y257. The E291G mutation might enable the free rotation of Y257, which might in turn destabilize the backbone of the loop formed by residues 223 to 226, rendering more mobility to F224 and, hence, reducing the affinity for BPIP and VP32947. It is concluded that a single drug-binding pocket exists within the finger domain region of the BVDV RdRp that consists of two separate but potentially overlapping binding sites rather than two distinct drug-binding pockets. (+info)Concurrent peste des petits ruminants virus and pestivirus infection in stillborn twin lambs. (8/25)
(+info)Pestivirus infections refer to a group of diseases caused by viruses of the genus Pestivirus, which belongs to the family Flaviviridae. There are several different types of Pestiviruses, including bovine viral diarrhea virus 1 and 2 (BVDV-1 and BVDV-2), classical swine fever virus (CSFV), and border disease virus (BDV).
These viruses can cause a range of clinical signs in animals, depending on the species infected, the age and immune status of the animal, and the strain of the virus. In general, Pestivirus infections can cause fever, lethargy, loss of appetite, and various symptoms related to the respiratory, digestive, or reproductive systems.
For example, BVDV-1 and BVDV-2 are important pathogens in cattle and can cause a variety of clinical signs, including respiratory disease, diarrhea, reproductive failure, and immunosuppression. CSFV is a highly contagious virus that affects pigs and can cause fever, loss of appetite, hemorrhages, and neurological symptoms. BDV infects sheep and goats and can cause abortion, stillbirth, and congenital defects in offspring.
Prevention and control measures for Pestivirus infections include vaccination, biosecurity practices, and testing and culling of infected animals.
Pestivirus is a genus of viruses in the family Flaviviridae, which are enveloped, single-stranded, positive-sense RNA viruses. There are several species within this genus that can cause disease in animals, including bovine viral diarrhea virus (BVDV) in cattle, border disease virus (BDV) in sheep, and classical swine fever virus (CSFV) in pigs. These viruses can cause a range of clinical signs, including respiratory and enteric diseases, reproductive failures, and immunosuppression. They are primarily spread through direct contact with infected animals or their bodily fluids, and can also be transmitted through contaminated fomites and semen. Prevention and control measures include vaccination, biosecurity practices, and testing and culling of infected animals.
Bovine viral diarrhea (BVD) is a viral disease that primarily affects cattle, but can also infect other ruminants such as sheep and goats. The disease is caused by the bovine viral diarrhea virus (BVDV), which belongs to the family Flaviviridae and genus Pestivirus.
There are two biotypes of BVDV, type 1 and type 2, which can be further divided into various subtypes based on their genetic makeup. The virus can cause a range of clinical signs in infected animals, depending on the age and immune status of the animal, as well as the strain of the virus.
Acute infection with BVDV can cause fever, lethargy, loss of appetite, nasal discharge, and diarrhea, which can be severe and life-threatening in young calves. In addition, BVDV can cause reproductive problems such as abortion, stillbirth, and the birth of persistently infected (PI) calves. PI animals are those that were infected with BVDV in utero and have the virus continuously present in their bloodstream and other tissues throughout their lives. These animals serve as a source of infection for other cattle and can spread the virus to naive herds.
BVDV is transmitted through direct contact with infected animals or their bodily fluids, such as saliva, nasal secretions, and feces. The virus can also be spread indirectly through contaminated feed, water, and equipment. Prevention and control measures for BVDV include biosecurity practices, vaccination, and testing to identify and remove PI animals from herds.
Classical Swine Fever Virus (CSFV) is a positive-stranded RNA virus that belongs to the genus Pestivirus within the family Flaviviridae. It is the causative agent of Classical Swine Fever (CSF), also known as hog cholera, which is a highly contagious and severe disease in pigs. The virus is primarily transmitted through direct contact with infected animals or their body fluids, but it can also be spread through contaminated feed, water, and fomites.
CSFV infects pigs of all ages, causing a range of clinical signs that may include fever, loss of appetite, lethargy, weakness, diarrhea, vomiting, and respiratory distress. In severe cases, the virus can cause hemorrhages in various organs, leading to high mortality rates. CSF is a significant disease of economic importance in the swine industry, as it can result in substantial production losses and trade restrictions.
Prevention and control measures for CSF include vaccination, biosecurity practices, and stamping-out policies. Vaccines against CSF are available but may not provide complete protection or prevent the virus from shedding, making it essential to maintain strict biosecurity measures in pig farms. In some countries, stamping-out policies involve the rapid detection and elimination of infected herds to prevent the spread of the disease.
Border Disease Virus (BDV) is a member of the genus Pestivirus within the family Flaviviridae. It is a viral pathogen that primarily affects sheep and goats, causing a disease known as Border Disease in these animals. The virus is named after the geographical location where it was first identified, the border region between England and Scotland.
BDV is a small, enveloped, single-stranded RNA virus that can cause a range of clinical signs in infected sheep and goats, including abortion, stillbirths, congenital defects, and poor growth rates in newborn lambs or kids. The virus is transmitted horizontally through direct contact with infected animals, their bodily fluids, or contaminated objects. Vertical transmission from ewes to their offspring can also occur, resulting in the birth of persistently infected (PI) lambs that serve as a significant source of infection within flocks.
Infection with BDV can lead to economic losses for farmers due to reduced productivity and increased mortality rates. There is no specific treatment for Border Disease, but vaccination programs can help control the spread of the virus in sheep and goat populations.
Bovine Viral Diarrhea Virus 1 (BVDV-1) is a species of the Pestivirus genus within the Flaviviridae family. It is a small, enveloped, single-stranded RNA virus that primarily affects cattle, causing a wide range of clinical signs including diarrhea, fever, lethargy, respiratory and reproductive problems. The virus can be transmitted through direct contact with infected animals or their bodily fluids, as well as indirectly through contaminated objects or environments. BVDV-1 infection can result in acute or persistent infections, with the latter being particularly detrimental to the health and productivity of affected herds.
It's worth noting that while diarrhea is a common symptom of BVDV-1 infection, it is not exclusively associated with this virus, and other causes should also be considered when diagnosing and managing cases of diarrhea in cattle.