| Bovine papular stomatitis virus | |
|---|---|
 | |
| Photograph of BPSV infection in dairy cattle from Siranjganj. Panel (A) shows parapoxvirus lesion on the teat of animal. Panel (B) shows erosions on the gingiva | |
Virus classification | |
| (unranked): | Virus |
| Realm: | Varidnaviria |
| Kingdom: | Bamfordvirae |
| Phylum: | Nucleocytoviricota |
| Class: | Pokkesviricetes |
| Order: | Chitovirales |
| Family: | Poxviridae |
| Genus: | Parapoxvirus |
| Species: | Parapoxvirus bovinestomatitis |
| Synonyms[1] | |
| |
Bovine papular stomatitis is azoonoticfarmyard pox caused by Bovine papular stomatitis virus (BPSV), which can spread from infected cattle to cause disease in milkers, farmers and veterinarians.[2] Generally there are usually one or multiple skinlesions, typically on the hands or forearm.[2] The disease is generally mild.[3]
BPSV is a member of the familyPoxviridae and the genusParapoxvirus.Spread typically occurs by direct contact with the infected animal, but has been reported in people without direct contact.[2] BPSV may appear similar tofoot-and-mouth disease.[3] It has been found to exhibit a size of around 320 nm by 190 nm, slightly larger than a typical parapoxvirus. BPSV exhibits an egg-like shape.[4]
It occurs worldwide incattle.[2] Most notably in conditions where cattle are in close contact with one another and in high-stress environments, such as fattening facilities.[5] In other animals the lesions are reddish, raised, sometimes ulcerative lesions on the lips, muzzle, and in the mouth. It usually occurs before the age of two years.[6]
The most common signs of BPSV in cattle are raised, erosive lesions around the muzzle, lips, cheek linings, and udders.[7] During post-mortem examinations, they have also been found further down the digestive tract (such as in therumen,reticulum, andomasum).[8]
Immunocompromised animals may exhibit a systemic version of the disease, displaying virus particles in their blood or lymphatic systems.[8] These nodules exhibit thickening of the skin (hyperkeratosis). Inflammation andedema have also been observed.[8]
Lesions can be found to be about the size of a soybean, though they often vary in size. Secondary bacterial infections and ulceration on or around these lesions can also be found.[8]
BPSV likely causes some form of persistent infection or frequent reinfections. Studies show recurrence rates of up to 53% over several years in different cattle groups.[7] One survey revealed that the majority of oral swabs from healthy calves indicated a positive result for BPSV DNA. Researchers suggest that many cattle are infected- though they may beasymptomatic and act as reservoirs for the virus.[7]
The severity of BPSV in humans is understood to be minimal.[9] Humans who frequently work in the dairy industry can come into contact with BPS lesions and sometimes develop lesions of their own, usually on the hands and fingers.[10] These lesions are often referred to as "milker's nodules",[4] "udder pox", or "milker's nodes"[5] and appear similar toOrf virus lesions.[4]
Frequency in humans is poorly understood. Overall, BPSV is reported to be a neglected zoonoses due to its lack of severity.[4] It is often generalized among the other parapoxviruses in human medicine, therefore leading to a lack of specific evidence pertaining specifically to BPSV.[5]
Students at theAuburn University College of Veterinary Medicine showed clinical signs of the virus in the late 1970s. Five individuals (students and faculty members) at the university were exposed to and possibly contracted BPSV- sparking the development a surveillance program to determine the frequency of the disease.[9]
The surveillance program extended over a 12-month period, involving 115 students. The students were asked about their frequency of exposure to bovine mouths, where 59 out of the 115 students confirmed frequent exposure- most of the students who reported frequent exposure were involved in large animalanesthesiology, where intubation and other oral contact is commonplace. 2 of the 59 students with frequent exposure reported probable BPSV cases, with the lesions reported to be "uncomplicated" and "scarce". However, within the same group of 115 students, 2 were reported to have hadbrucellosis infections, and 5 had been exposed torabies. Due to the infrequency and uncomplicated nature of BPSV in veterinary students, the occurrence of BPSV in humans was reported to be "low on the list of zoonoses in terms of public health importance."[9]
Nuclei in the epithelial cells of BPSV nodules have shownpyknosis andkaryorrhexis.[8] BPSV affects keratinocytes of the stratum spinosum layer of the epidermis, causing ballooning, vacuolation, and erosive dermatitis.[11] Infected cells often display cytoplasmic inclusion bodies when stained withhematoxylin-eosin stain. Cells in the spinosum layer can also display granular "eosinophilic" or "basophilic" characteristics.[8]
The BPSV genome encodes for a viralvascular endothelial growth factor (vVEGF), which are unique to BPSV, Orf viruses, andpseudocowpoxvirus (PCPV).[12] vVEGFs mimic host vascular factors that bind toreceptor tyrosine kinase enzymes and include N- and O- linked glycosylation sites, uniquecystine knot motifs, andaspartic acid residues that bind specifically to VEGF receptors.[12] vVEGFs affecttumor development andembryogenesis.[12]
BPSV-CBP interacts with inflammatorychemokines that attractmonocytes anddendritic cells (DCs) to inflamed skin, as well as constitutivechemokines involved in the movement ofantigen-presenting cells within lymphoid tissue.[11] It also bound CXC chemokines (linked toneutrophil recruitment) and the lymphotactin chemokine XCL1, which drawsT cells to the site of infection.[11]
Compared to type II chemokine binding proteins (CBPs) fromOrthopoxviruses and Leporipoxviruses, BPSV-CBP exhibits a broader binding spectrum, including CC, CXC, and XC chemokines.[11] This divergence hints at an evolutionary path that has allowed Parapoxvirus-CBPs (PPV-CBPs) to develop this broader interaction capability, which is also seen in someherpesviruses.[11]
The recruitment of various immune cells, such as monocytes,NK cells,mast cells, and neutrophils, is critical for immune defense against viral pathogens.[11] It remains uncertain how effective BPSV-CBP is against neutrophil-mediated defense mechanisms.
BPSV-CBP likely inhibits cell trafficking in infected hosts, potentially delaying adaptive immune responses.[11]
One study showed that BPSV-CBP significantly inhibited neutrophil infiltration in a skin inflammation model, although this effect was temporary.[11] The study states that poxviruses utilize unique chemokine-binding strategies to evade the robust immune response of the skin, a primary barrier against infection.[11] By dampening inflammation and shielding infected cells, BPSV-CBP may contribute to persistent infections.[11] The ability of BPSV-CBP to modulate neutrophil responses indicates its potential as an anti-inflammatory agent, though it may need to be used alongside other treatments to effectively manage inflammation in skin disorders.[11]
BPSV has several advantageous features for use in a viral vector vaccine:
BPSV has been used in an experiment involving Bovine Herpesvirus 1 (BoHV-1) to observe the potential for BPSV as a viral vector. BoHV-1 has 3 main envelopeglycoproteins (gB, gD, and gC) that, when reactivated after alatent period, induce a targeted immune response.[7] Researchers in this study created arecombinant BPSV-C5 strain that contained a modified BoHV-1 gD gene and was able to inhibit theNF-κB pathway, a crucial process during viral infection.[7] Researchers inserted a modified BoHV-1 gB gene into the BPSVgD virus.[7] Genetic alterations were not indicated to hinder viral replication, as both BPSVgD and the BPSVgD/gB virus showed replication rates similar to wild-type BPSVin vitro.[7]
In the same experiment, ovine fetal turbinate (OFTu) cells were either uninfected or infected with BPSVgD/gB and examined using antibody-flagged immunofluorescence.[7] Western blot analysis confirmed that the BPSVgD/gB virus successfully expressed both BoHV-1 glycoproteins.[7] Results indicated that the BPSVgD strain was non-virulent, but BoHV-1 antibody titers were elevated for weeks following inoculation.[7] No adverse effects were recorded with the use of the BPSVgD or BPSVgD/gB strains.[7]