Bovine Herpesvirus Research Articles

Global overview on treatment COVID-19 in humans with ivermectin

Given the urgency of the ongoing COVID-19 pandemic, its complications and deaths, the discovery of new mutated strains and the potential for re-emergence of novel coronaviruses, the reuse of drugs such as ivermectin may deserve attention. This review article aims to discuss the potential mechanisms of action of ivermectin against SARS-CoV-2, and COVID-19 by summarizing the available literature since the onset of the disease. Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients In this comprehensive systematic review, multiple studies have reported that ivermectin exhibits antiviral properties against a wide range of RNA viruses, including Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, some studies have indicated that ivermectin also shows antiviral effects against DNA viruses, such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin's antiviral actions are attributed to its involvement in various biological mechanisms, suggesting its potential as a candidate for treating a wide array of viruses, including COVID-19, and other positive-sense single-stranded RNA viruses. This systematic review encompasses evidence dating back to 1970, underscoring ivermectin's capacity to combat a diverse array of viral infections. The findings of this study suggest that ivermectin might serve as a valuable antiviral agent for viruses, especially those with positive-sense single-stranded RNA genomes. Notably, experimental studies have shown significant effectiveness when ivermectin is administered during the early stages of infection, which implies its potential in early treatment or prevention. However, it's important to note that confirming these assertions requires human studies and clinical trials.

Bovine Respiratory Disease Complex: Prevalence of the Main Respiratory Viruses Involved in Pneumonia in Spain

The most common cause of disease among cattle is Bovine Respiratory Disease, and its control has a great impact on the profitability of cattle farms. It is a multifactorial and polymicrobial complex, involving both bacteria and viruses. The objective of this study was to assess the prevalence of the most relevant bovine respiratory viruses (bovine viral diarrhoea, bovine herpesvirus type 1, and bovine respiratory syncytial viruses) due to their clinical relevance, and also their course over time to facilitate decision-making when designing vaccination programmes based on scientific evidence. Samples from animals with early symptoms of respiratory disease were taken using the BOVIRESPCHECK kit, enabling nasal swabs to be taken from four different animals within the same farm. The samples were analysed separately for each animal (not pooled) for the detection of the three viruses by real time polymerase chain reaction. Between 2016 and 2020, a total of 964 reports were created, from a total of 661 cattle farms distributed all over Spain. Each report corresponds to a farm that had an outbreak or respiratory problem at the time. The most frequently detected virus was bovine respiratory syncytial virus, present in 31.5% of the reports, followed by bovine viral diarrhoea virus detected in 23.94% of them. Both viruses were found in combination in 15.96% of cases, showing a significant positive correlation between them. The bovine herpesvirus type 1 was detected in 17.2% of reports; however, the prevalence reached a peak at 28.11% in 2020 with the restriction in use of multivalent (non-marker) vaccines in the country. These results underline the significance of implementing complete vaccination programmes that cover all the most important respiratory viruses. Vaccination against bovine respiratory syncytial and bovine viral diarrhoea viruses seems to be justifiable not only because of the high incidence of both pathogens, but also because of the positive correlation between them. The use of infectious bovine rhinotracheitis monovalent marker vaccines should be added to the above-mentioned vaccines, as their exclusion could be partly responsible for the increased incidence of the bovine herpesvirus type 1 and its associated pathology in 2020. There is a need for a multivalent vaccine including the most relevant viruses with an IBR-marker component to control BRD.

Descriptive cross-sectional study on major bovine diseases and associated risk factors in north-eastern Ecuadorian Amazon.

Cattle raising is a crucial element of production systems in the tropics and subtropics. However, in recent years, global public health security has been threatened by disease emergence. In Orellana Province, livestock is the most important activity to generate economic income. Nevertheless, there is no available data about Animal Health status. With this objective, a study was performed to describe the major Bovine diseases recorded between 2011 to 2019, and the main Risk factors associated. Data on main Bovine diseases were retrieved from the World Animal Health Information System database. Whereas Bovine population data used to calculate the prevalence rates and confidence intervals were obtained from Ecuador's Ministry of Agriculture. By contrast, the Risk factors identified with an epidemiological questionnaire were applied to 300 livestock farmers. As a result, from 2011 to 2019 in Orellana has been confirmed: 90 cases of Infectious Bovine Rhinotracheitis (31.58%), Bovine Rabies by hematophagous bats (Desmodus rotundus), 83 cases (29.12%), Bovine viral diarrhea with 43 cases (15.10%), Brucellosis by Brucella abortus 35 cases, which was (12.28%), and 34 cases related to Enzootic bovine leukosis (11.92%). Overall, the prevalence rates ranged from (0.24 to 15.37%). In addition, farm size, presence of forest, herd, and paddock sizes, cutting frequency of forages, and other animal species were involved as Risk factors (OR = 3.15 to 11.75; 95% CI, 0.01 to 0.69). In conclusion, there are animal diseases with reproductive and neurologic symptomology and high-Risk factors implicated in the transmission. Consequently, space-temporal and seroprevalence epidemiological studies should be performed in Orellana.

Detection of bovine viral diarrhea virus and bovine herpes virus type 1 in cattle with and without endometritis.

This study aimed to investigate the potential presence of bovine herpes virus type 1 (BHV-1) and bovine viral diarrhea virus (BVDV) in cattle uteri that did not display any clinical and macroscopic signs of infection. Virus detection involved polymerase chain reaction (PCR) test, double immunohistochemistry (IHC), and double immunofluorescence (IF). One hundred cornu uterus samples were collected from cattle aged 1 year and older. The BVDV was detected by PCR or by double IHC/IF in the collected samples from slaughterhouses in Kayseri city (Central Anatolia, Türkiye) from 2021 - 2022. By contrast, BHV-1 was detected by PCR and double IHC/IF at a rate of 16.00% and 21.00%, respectively. In the IHC and IF detection, BHV-1 was detected in endometrial epithelial cells and in some mononuclear cells in the lamina propria, periglandular areas and myometrium. Although no macroscopic lesion was found in the BHV-1-positive samples (n = 21), histopathological detection showed that two had acute endometritis, eight had subacute endometritis, eight had chronic endometritis and the three others showed no signs of endometritis. This prevalence study demonstrated for the first time that even while BVDV could not be detected in the samples, BHV-1 posed a critical potential reproductive risk in pregnant animals, as it can specifically cause abortions when it resides in cattle uteri that do not show clinical or macroscopic and even microscopic signs of infection. Additionally, this study was the first to combine PCR and double IHC/IF for BHV-1 and BVDV detection in cattle uteri.

The influence of passive colostrum transfer on humoral immunity to selected antigens of Mannheimia haemolytica in calves

The aim of the study was to evaluate the effectiveness of colostral immunity against aetiological agents of bovine respiratory disease complex (BRDC), to assess the suppressive effect of colostral antibodies against Mannheimia haemolytica on immunity, and to analyse acute phase proteins in calves. Holstein-Friesian and Simmental cows and calves were immunized with M. haemolytica leukotoxin (Lkt) and outer membrane proteins (OMPs) at 6 and 4 weeks before parturition. Sera and colostrum were collected from the cows directly after calving. Sera from calves were obtained before colostrum intake and 48 h after birth. Calves from vaccinated and unvaccinated cows were placed in the feedlot and immunized with Lkt or OMP on days 10 and 24. Calves were tested for serum antibodies against respiratory viruses. Trachea and lung samples were collected for bacteriological examination from all calves that had died with BRDC. The results indicated high colostrum values and IgG transfer in calves at 48 h (> 12.5 g/l) and a high concentration of anti-BVD antibodies in calves at 48 h (> 33–45 mg/ml). Similar values were observed for bovine herpes virus BHV-1 and bovine respiratory sycytil virus BRSV. Immunoglobulin concentrations were highest for antibodies specific to parainfluenza PI-3 and adenoviruses. The lowest antibody levels were detected against M. haemolytica antigens in all experimental groups of calves (< 50 mg/ml in calves of cows vaccinated with M. haemolytica antigens and < 25 mg/ml in calves of unvaccinated cows). The findings indicate the need for early immunization of calves, which is often precluded by stress associated with transport and adaptation to the new conditions in the feedlot.

Pathogenic infection characteristics and risk factors for bovine respiratory disease complex based on the detection of lung pathogens in dead cattle in Northeast China.

Bovine respiratory disease complex (BRDC) involves multiple pathogens, shows diverse lung lesions, and is a major concern in calves. Pathogens from 160 lung samples of dead cattle from 81 cattle farms in Northeast China from 2016 to 2021 were collected to characterize the molecular epidemiology and risk factors of BRDC and to assess the major pathogens involved in bovine suppurative or caseous necrotizing pneumonia. The BRDC was diagnosed by autopsy, pathogen isolation, PCR, or reverse transcription-PCR detection, and gene sequencing. More than 18 species of pathogens, including 491 strains of respiratory pathogens, were detected. The positivity rate of bacteria in the 160 lung samples was 31.77%, including Trueperella pyogenes (9.37%), Pasteurella multocida (8.35%), Histophilus somni (4.48%), Mannheimia haemolytica (2.44%), and other bacteria (7.13%). The positivity rate of Mycoplasma spp. was 38.9%, including M. bovis (7.74%), M. dispar (11.61%), M. bovirhinis (7.94%), M. alkalescens (6.11%), M. arginini (0.81%), and undetermined species (4.68%). Six species of viruses were detected with a positivity rate of 29.33%, including bovine herpesvirus-1 (BoHV-1; 13.25%), bovine respiratory syncytial virus (BRSV; 5.50%), bovine viral diarrhea virus (BVDV; 4.89%), bovine parainfluenza virus type-3 (BPIV-3; 4.28%), bovine parainfluenza virus type-5 (1.22%), and bovine coronavirus (2.24%). Mixed infections among bacteria (73.75%), viruses (50%), and M. bovis (23.75%) were the major features of BRDC in these cattle herds. The risk analysis for multi-pathogen co-infection indicated that BoHV-1 and H. somni; BVDV and M. bovis, P. multocida, T. pyogenes, or Mann. haemolytica; BPIV-3 and M. bovis; BRSV and M. bovis, P. multocida, or T. pyogenes; P. multocida and T. pyogenes; and M. bovis and T. pyogenes or H. somni showed co-infection trends. A survey on molecular epidemiology indicated that the occurrence rate of currently prevalent pathogens in BRDC was 46.15% (6/13) for BoHV-1.2b and 53.85% (7/13) for BoHV-1.2c, 53.3% (8/15) for BVDV-1b and 46.7% (7/15) for BVDV-1d, 29.41% (5/17) for BPIV-3a and 70.59% (12/17) for BPIV-3c, 100% (2/2) for BRSV gene subgroup IX, 91.67% (33/36) for P. multocida serotype A, and 8.33% (3/36) for P. multocida serotype D. Our research discovered new subgenotypes for BoHV-1.2c, BRSV gene subgroup IX, and P. multocida serotype D in China's cattle herds. In the BRDC cases, bovine suppurative or caseous necrotizing pneumonia was highly related to BVDV [odds ratio (OR) = 4.18; 95% confidence interval (95% CI): 1.6-10.7], M. bovis (OR = 2.35; 95% CI: 1.1-4.9), H. somni (OR = 8.2; 95% CI: 2.6-25.5), and T. pyogenes (OR = 13.92; 95% CI: 5.8-33.3). The risk factor analysis found that dairy calves <3 mo and beef calves >3 mo (OR = 5.39; 95% CI: 2.7-10.7) were more susceptible to BRDC. Beef cattle were more susceptible to bovine suppurative or caseous necrotizing pneumonia than dairy cattle (OR = 2.32; 95% CI: 1.2-4.4). These epidemiological data and the new pathogen subgenotypes will be helpful in formulating strategies of control and prevention, developing new vaccines, improving clinical differential diagnosis by necropsy, predicting the most likely pathogen, and justifying antimicrobial use.

Epidemiological investigation on Bovine alphaherpesvirus 1 and bovine viral diarrhea virus in cattle and camels in southern Egypt.

In this study, the ELISA procedure was used to detect antibodies against bovine viral diarrhea (BVDV) and infectious bovine rhinotracheitis (IBRV) viruses. The BVDV serological survey in Aswan province in southern Egypt was carried out on 184 unvaccinated cattle and camels. The overall seroprevalence was 18.48% (34/184), but in cattle was 34.78% (32/92) and 2.18% (2/92) in camels. The serological survey was conducted on infectious bovine rhinotracheitis virus (IBRV) antibodies was conducted on 460 unvaccinated cattle from three different provinces (Qena, Luxor, and Aswan). The overall seroprevalence was 60.00% (276/460). The infection rate in Aswan was higher (83.70%) than Qena and Luxor, 53.63% and 45.65%, respectively. Epidemiological status was established to clarify the influence of location in Qena, Luxor and Aswan for bovine viral diarrhea and infectious bovine rhinotracheitis and the effect of management systems in infection rate for cattle. The high predominance of antibodies in cattle may be the principal factor to limit the cattle industry in Egypt. This study aims to investigate the seroprevalence rate of Bovine alphaherpesvirus 1 and bovine viral diarrhea in cattle and camel in southern Egypt.

Seroprevalence of Infectious bovine rhinotracheitis (IBR) in India: A 5-year study.

Infectious bovine rhinotracheitis (IBR) is a highly contagious disease of bovines causing respiratory symptoms, abortions, and reduced milk yield, leading to huge economic losses. Reports on seroprevalence in bovines in India are available and restricted to districts/states. In the present study, a nationwide seroprevalence of IBR in bovines was conducted to provide a national IBR seroprevalence to the Chief Veterinarian who in turn can design the control strategies. A total of 15,592 cattle and buffalo serum samples from 25 states and 3 Union Territories viz., Jammu and Kashmir, Puducherry, and Andaman and Nicobar Islands were tested for IBR antibodies using Avidin‑Biotin (AB) ELISA. Cumulative seropositivity was found to be 31.37%. Maharashtra and Rajasthan states, part of the west zone of the country, showed the highest and lowest seroprevalence, respectively. A total of 11,423 cattle and 4,169 buffalo serum samples were tested, which showed 33.91% and 24.39% seropositivity, respectively. India has the highest buffalo population. Presently, India no IBR vaccination programs are implemented in India. Considering the high seroprevalence, the authorities should plan control strategies for vaccinating dairy cows and buffaloes in India.

First isolation and characterization of Bovine Herpesvirus 1.2b (BoHV-1.2b ) strain from respiratory tract of cattle in Turkey

Restriksiyon Parça Uzunluk Polimorfizmi (RFLP) tekniği kullanılarak tüm genomun analizinde Bovine Herpesviruses-1 (BoHV-1) suşlarını BoHV-1.1, 1.2a, 1.2b olmak üzere üç alt tipte sınıflandırılmaktadır. Bu alt tipler klinik bulgular göre de değerlendirilmektedir ancak bu yönde henüz net bir ilişkilendirme yapılmamıştır. Çoğunlukla BoHV-1.2b, genital hastalık bulgularıyla ilişkilendirilmektedir. Bu çalışmada solunum yolu hastalığından alınan nazal sürüntü örneğinde BoHV-1 izolatı elde edilmiştir. Bu çalışmada ayrıca, genomun UL44 (Glikoprotein C) bölgesini hedefleyen filogenetik analiz ve UL39 - US3 bölgelerini hedefleyen, yeni geliştirilen bir multipleks PCR analizini takiben Hind III enzimi kullanılarak uygulanan RFLP ile alt tiplendirme gerçekleştirilmiştir. Aynı zamanda izolasyon başarısı iki farklı devamlı hücre hattında karşılaştırılmıştır. SFT-R hücre hattı, BoHV-1 saha örneklerinin izolasyonunda MDBK hücre hattına nazaran daha duyarlı bulunmuştur. Elde edilen izolat (ID:8640), BoHV-1.2b olarak sınıflandırılırken, Cooper suşundan serolojik olarak ayırt edilemediği değerlendirildi. Mevcut çalışma, BoHV-1.2b'nin Türkiye'deki ilk izolasyonunu bildirmesinin yanı sıra klinik solunum yolu hastalığından nadir tespit edilen BoHV-1.2b izolasyonunu bildirmektedir. Sonuçlar ayrıca kolay ve hızlı alt tipleme için PCR tabanlı RFLP analizinin etkinliğini gösteren veriler içermektedir. Ancak BoHV-1 saha izolatlarının genetik çeşitliliğine bağlı olarak bu teknik üzerine daha fazla araştırma yapılmasına ihtiyaç duyulmaktadır.

Prevalence of bovine herpesvirus 1 antibodies and risk factors in dairy cattle of Iran’s central desert

Bovine herpesvirus type 1 (BoHV 1) is a major bovine pathogen spreading worldwide and causing extensive damage to the livestock industry. BoHV causes respiratory, genital, and neurological disorders. A cross-sectional study was performed for the first time to estimate the seroreactivity to BoHV 1 and related risk factors among Iran's central desert dairy cattle. A total of 800 blood samples was randomly collected from 76 unvaccinated herds. Samples were tested with an indirect enzyme-linked immunosorbent assay (ELISA) commercial kit to detect BoHV 1 antibodies. The logistic regression model was used to analyze the data. BoHV 1 seroreactivity at animal and herd levels was 50% and 65%, respectively. Herd size was recognized as a risk factor (OR = 2.65, CI = 1.61-4.37) for seroreactivity to BoHV using GLM (p < 0.05). The high prevalence of BoHV 1 antibodies in the study area indicates the need to implement educational programs on the importance of the disease and design methods to control and prevent virus distribution.

Sexual Dimorphic Innate Immune Response to a Viral-Bacterial Respiratory Disease Challenge in Beef Calves.

The potential for sexually dimorphic innate immune responses to respiratory disease was evaluated, where eight steers and seven heifers (280 ± 4 kg) were subjected to a viral-bacterial respiratory disease challenge utilizing bovine herpesvirus-1 (BoHV-1; intranasal; 1 × 108 PFU/nostril) and Mannheimia haemolytica (MH; intratracheal; 1.3 × 107 CFU/head) administered 72 h later. Body temperature was lesser in heifers than steers (p &lt; 0.01). There was a sex × time interaction (p = 0.05) for white blood cells where heifers had reduced concentrations compared with steers at -72 and 0 h but greater concentrations from 36 to 60 h post-MH. Concentrations of neutrophils were lesser in heifers compared to steers from 0 to 4 h, and from 8 to 12 h (p = 0.03). Lymphocytes were greater in heifers compared to steers at 12 h and from 36 to 60 h post-MH (p &lt; 0.01). The neutrophil-lymphocyte ratio was lesser in heifers compared to steers from 2 to 24 h and at 48 h post-MH (p &lt; 0.01). Monocytes were greater in heifers compared to steers from 24 to 60 h post-MH (p &lt; 0.01), while eosinophils were greater in heifers compared to steers at 48 and 60 h (p &lt; 0.01). Serum IL-4 was lesser in heifers compared to steers at 0 h and from 2 to 72 h post-MH challenge (p = 0.02). Non-esterified fatty acid concentrations were lesser (p &lt; 0.01) in heifers compared to steers from 2 to 4 h post-MH challenge. Urea nitrogen concentrations were greater (p &lt; 0.01) in heifers than steers at 36 h post-MH challenge. Data from this study reveal distinct differences in the acute phase response following a respiratory disease challenge where steers produced an early response, while the response in heifers appeared to be delayed.

Phospholipase C-γ1 potentially facilitates subcellular localization of activated β-catenin, p-β-catenin(S552), during bovine herpesvirus 1 productive infection in MDBK cells

Bovine herpesvirus 1 (BoHV-1) is a significant risk factor for the bovine respiratory disease complex (BRDC), a severe disease causing great economic losses to the cattle industry worldwide. Previous studies have reported that both phospholipase C-γ1 (PLC-γ1) and β-catenin are activated during BoHV-1 infection for efficient replication. However, the interplay between PLC-γ1 and β-catenin as a consequence of virus infection remains to be elucidated. Here, we reported that PLC-γ1 interacted with β-catenin, which was enhanced following virus infection. PLC-γ1-specific inhibitor, U73122, significantly reduced the mRNA levels of β-catenin in BoHV-1-infected cells; however, the steady-state protein levels were not affected due to the virus infection. Interestingly, the treatment of virus-infected cells with U73122 reduced the accumulation of activated β-catenin [p-β-catenin(S552)] in fractions of the cytoplasmic membrane as that observed with the treatment of methyl-β-cyclodextrin (MβCD), which can disrupt cytoplasmic membrane structure via sequestering cholesterol. Nucleus accumulation of p-β-catenin(S552) was increased following U73122 treatment in virus-infected cells. In addition, the association of p-β-catenin(S552) with cytoplasmic membrane induced by the virus infection was significantly disrupted by the treatment of U73122 and MβCD. These data indicated that the PLC-γ1 signaling is potentially involved in the regulation of β-catenin signaling stimulated by BoHV-1 infection partially via affecting the subcellular localization of p-β-catenin(S552).

Influenza D Virus: A Review and Update of Its Role in Bovine Respiratory Syndrome

Bovine respiratory disease (BRD) is one of the most prevalent, deadly, and costly diseases in young cattle. BRD has been recognized as a multifactorial disease caused mainly by viruses (bovine herpesvirus, BVDV, parainfluenza-3 virus, respiratory syncytial virus, and bovine coronavirus) and bacteria (Mycoplasma bovis, Pasteurella multocida, Mannheimia haemolytica and Histophilus somni). However, other microorganisms have been recognized to cause BRD. Influenza D virus (IDV) is a novel RNA pathogen belonging to the family Orthomyxoviridae, first discovered in 2011. It is distributed worldwide in cattle, the main reservoir. IDV has been demonstrated to play a role in BRD, with proven ability to cause respiratory disease, a high transmission rate, and potentiate the effects of other pathogens. The transmission mechanisms of this virus are by direct contact and by aerosol route over short distances. IDV causes lesions in the upper respiratory tract of calves and can also replicate in the lower respiratory tract and cause pneumonia. There is currently no commercial vaccine or specific treatment for IDV. It should be noted that IDV has zoonotic potential and could be a major public health concern if there is a drastic change in its pathogenicity to humans. This review summarizes current knowledge regarding IDV structure, pathogenesis, clinical significance, and epidemiology.

A neutralizing monoclonal antibody-based blocking ELISA to detect bovine herpesvirus 1 and vaccination efficacy.

Infections caused by bovine herpesvirus 1 (BoHV-1) remain a serious global issue to the health and welfare of the bovine industry. Monitoring of neutralizing antibodies is essential not only for epidemic diagnosis, but also to assess vaccination efficacy. In this study, we generated a neutralizing monoclonal antibody, termed as 3F8, targeting glycoprotein D (gD) of BoHV-1. This monoclonal antibody could neutralize BoHV-1 with a 50% inhibitory concentration (IC50) of 37.82ng/mL. Furthermore, 3F8 could inhibit BoHV-1 infection and cell-to-cell spread at the prebinding stage. A blocking enzyme-linked immunosorbent assay (ELISA) for detecting neutralizing antibodies against BoHV-1 was then developed based on 3F8 and protein gD generated using a baculovirus expression system. The sensitivity and specificity of the test were estimated to be 94.59% and 93.42%, respectively. A significant correlation (R2 = 0.9583, p < 0.01) was observed between the results obtained with the blocking ELISA and a virus neutralization test, which suggested that the blocking ELISA could detect neutralizing antibodies against BoHV-1. A serological survey was carried out in the dairy farms in Beijing district using 3F8-based blocking ELISA to monitor the annual neutralization antibody against BoHV-1 during 2012-2020. It revealed that the dairy farms in Beijing were at high risk of BoHV-1 infection during 2012-2017 but were protected since 2018 upon implementation of an immunization program. Our results demonstrated that this assay is suitable for BoHV-1 surveillance and vaccination efficacy in cattle as a replacement for the virus neutralization test. KEY POINTS: • Prevention of BoHV-1 infection requires the monitoring of neutralizing antibodies. • A blocking ELISA for the neutralizing antibody was developedbased on mAb 3F8 against BoHV-1 gD. • It can replace the labor-intensive and time-consuming viral neutralizing tests.

Molecular Investigation of Bovine Viral Diarrhea Virus, Bovine Herpes Virus-1 and Bovine Herpes Virus-4 Infections in Abortion Cases of Cattle in Van District, Turkey

Abortions, fetal mummification, calf anomalies, and infertility problems constitute most of the reproductive problems in cattle. Viruses play a significant role in the cause of these cases. In cattle, these agents are known as primary abortion agents and the most common of these agents are Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus Type 1 (BoHV-1), and Bovine Herpes Virus Type 4 (BoHV-4). The objective of this research is to determine the potential role of BVDV, BoHV-1, and BoHV-4 as viral abortion agents in cattle housed in the Van district. For this, a total of 115 animal specimens (blood, serum, vaginal swab, vaginal fluid discharge, nasal swab, and abortion material) from 100 abortion, early embryonic deaths, and infertility cases in cattle over the age of 2-5 years old were collected. All samples for detection of BVDV, BoHV-1 and BoHV-4 genomes were tested by the Polymerase Chain Reaction (PCR) technique using specific primers encoding Panpesti 5'-UTR, Glycoprotein C (gC) and Glycoprotein B (gB) genes, respectively. Result out of the samples tested, 41.73% were positive for BVDV and all samples were negative for BoHV-1 and BoHV-4. In conclusion, the presence of BVDV in cattle in the Van region and its role in the occurrence of abortion cases was emphasized for the first time. It is necessary to the consideration of viral abortions and determine the etiology of abortion cases and genital system problems. According to this, we need to focus on the detection of persistently infected (PI) animals for prevention and control of infection and the most effective way of vaccinating susceptible populations.

Stress Triggers Expression of Bovine Herpesvirus 1 Infected Cell Protein 4 (bICP4) RNA during Early Stages of Reactivation from Latency in Pharyngeal Tonsil.

Bovine herpesvirus 1 (BoHV-1), an important pathogen of cattle, establishes lifelong latency in sensory neurons within trigeminal ganglia (TG) after acute infection. The BoHV-1 latency-reactivation cycle, like other alphaherpesvirinae subfamily members, is essential for viral persistence and transmission. Notably, cells within pharyngeal tonsil (PT) also support a quiescent or latent BoHV-1 infection. The synthetic corticosteroid dexamethasone, which mimics the effects of stress, consistently induces BoHV-1 reactivation from latency allowing early stages of viral reactivation to be examined in the natural host. Based on previous studies, we hypothesized that stress-induced cellular factors trigger expression of key viral transcriptional regulatory genes. To explore this hypothesis, RNA-sequencing studies compared viral gene expression in PT during early stages of dexamethasone-induced reactivation from latency. Strikingly, RNA encoding infected cell protein 4 (bICP4), which is translated into an essential viral transcriptional regulatory protein, was detected 30 min after dexamethasone treatment. Ninety minutes after dexamethasone treatment bICP4 and, to a lesser extent, bICP0 RNA were detected in PT. All lytic cycle viral transcripts were detected within 3 h after dexamethasone treatment. Surprisingly, the latency related (LR) gene, the only viral gene abundantly expressed in latently infected TG neurons, was not detected in PT during latency. In TG neurons, bICP0 and the viral tegument protein VP16 are expressed before bICP4 during reactivation, suggesting distinct viral regulatory genes mediate reactivation from latency in PT versus TG neurons. Finally, these studies confirm PT is a biologically relevant site for BoHV-1 latency, reactivation from latency, and virus transmission. IMPORTANCE BoHV-1, a neurotropic herpesvirus, establishes, maintains, and reactivates from latency in neurons. BoHV-1 DNA is also detected in pharyngeal tonsil (PT) from latently infected calves. RNA-sequencing studies revealed the viral infected cell protein 4 (bICP4) RNA was expressed in PT of latently infected calves within 30 min after dexamethasone was used to initiate reactivation. As expected, bICP4 RNA was not detected during latency. All lytic cycle viral genes were expressed within 3 h after dexamethasone treatment. Conversely, bICP0 and the viral tegument protein VP16 are expressed prior to bICP4 in trigeminal ganglionic neurons during reactivation. The viral latency related gene, which is abundantly expressed in latently infected neurons, was not abundantly expressed in PT during latency. These studies provide new evidence PT is a biologically relevant site for BoHV-1 latency and reactivation. Finally, we predict other alphaherpesvirinae subfamily members utilize PT as a site for latency and reactivation.

Effectiveness of the Fungal Metabolite 3-O-Methylfunicone towards Canine Coronavirus in a Canine Fibrosarcoma Cell Line (A72).

Canine coronavirus (CCoV), an alphacoronavirus, may cause self-limiting enteric disease in dogs, especially in puppies. The noteworthy plasticity of coronaviruses (CoVs) occurs through mutation and recombination processes, which sometimes generate new dangerous variants. The ongoing SARS-CoV-2 pandemic and the isolation of a novel canine-feline recombinant alphacoronavirus from humans emphasizes the cross-species transmission ability of CoVs. In this context, exploring antiviral compounds is essential to find new tools for fighting against CoVs infections. Fungi produce secondary metabolites, which are often developed as antibiotics, fungicides, hormones, and plant growth regulators. Previous examinations of benzo-γ-pyrone 3-O-methylfunicone (OMF), obtained from Talaromyces pinophilus, showed that it reduces the infectivity of hepatitis C virus and bovine herpesvirus 1. Based on this evidence, this study evaluated the antiviral ability of OMF against CCoV infection in a canine fibrosarcoma (A72) cell line. During CCoV infection, a non-toxic dose of OMF markedly increased features of cell viability. Moreover, OMF induced a significant reduction in virus yield in the presence of an intense downregulation of the viral nucleocapsid protein (NP). These findings occurred in the presence of a marked reduction in the aryl hydrocarbon receptor (AhR) expression. Taken together, preliminary findings suggest that OMF inhibiting AhR shows promising activity against CCoV infection.

Occurrence of Bovine Coronavirus and other Major Respiratory Viruses in Cattle in Poland.

Bovine coronavirus (BCoV) is a causative agent of enteric and respiratory diseases in cattle. Despite its importance for animal health, no data is available on its prevalence in Poland. The aim of the study was to determine the virus' seroprevalence, identify risk factors of BCoV exposure in selected cattle farms and investigate the genetic variability of circulating strains. Serum and nasal swab samples were collected from 296 individuals from 51 cattle herds. Serum samples were tested with ELISA for the presence of BCoV-, bovine herpesvirus-1 (BoHV-1)- and bovine viral diarrhoea virus (BVDV)-specific antibodies. The presence of those viruses in nasal swabs was tested by real-time PCR assays. Phylogenetic analysis was performed using fragments of the BCoV S gene. Antibodies specific to BCoV were found in 215 (72.6%) animals. Seropositivity for BCoV was more frequent (P>0.05) in calves under 6 months of age, animals with respiratory signs coinfected with BoHV-1 and BVDV and increased with herd size. In the final model, age and herd size were established as risk factors for BCoV-seropositivity. Genetic material of BCoV was found in 31 (10.5%) animals. The probability of BCoV detection was the highest in medium-sized herds. Polish BCoVs showed high genetic homology (98.3-100%) and close relatedness to European strains. Infections with BCoV were more common than infections with BoHV-1 and BVDV. Bovine coronavirus exposure and shedding show age- and herd density-dependence.

Expression of apoptosis-related genes at different stages of BoHV-1 and 5 infection of bovine neural tissue

Bovine alphaherpesviruses (BoHV) 1 and 5 share many genetic and structural characteristics; however, they differ in their ability to cause encephalitis. Previous research suggests that this difference might be caused by a differential modulation of apoptosis. In this study, we analyzed the mRNA expression of Bax, Bcl-2, Fas and caspases 3 and 8 in neural tissue sections of BoHV-1 and BoHV-5 experimentally-infected cattle. Overall, Fas and caspase 3 mRNA was up-regulated during BoHV-5 acute infection, latency, and reactivation. Conversely, caspase 3 mRNA levels increased only in the olfactory cortex during BoHV-1 acute infection, and it was down-regulated during reactivation, while Fas was only up-regulated during BoHV-1 acute infection and latency. Moreover, Bax/Bcl-2 ratio was lower than 1 during BoHV-1 acute infection except in the trigeminal ganglion, whereas many brain regions exhibit a ratio higher than 1 during BoHV-5 acute infection and reactivation. In summary, our findings suggest that during acute infection and reactivation, BoHV-5 induces a pro-apoptotic condition that could partially justify its increased ability to cause neurological damage.

The full-genome characterization and phylogenetic analysis of bovine herpesvirus type 1.2 isolated in China.

Bovine herpesvirus type 1 (BHV-1) causes bovine respiratory disease that poses a significant threat to the cattle industry. The prevalence of BHV-1 has recently increased in China. However, the lack of information about the prevalent isolates limits the control of the disease. In this study, a novel strain of BHV-1 was isolated from nasal swabs of Holstein cows in 2020 in China, designated as BHV SHJS. The genome of BHV strain SHJS is 135, 102 bp in length and highly similar to strain SP1777 (KM258883.1) with an identity of 99.64%. Mutations, insertions, or deletions mainly occur in UL27, UL44, and US8, etc., relative to the different genomic coordinates. Phylogenetic tree of UL44 (gC) showed that BHV strain SHJS belongs to BHV-1.2b cluster. The result showed that the strain had a different evolutionary origin from those prevalent in China. This study will enrich our knowledge regarding BHV outbreak strains in China and contribute to the prevention and pathogenic studies of BHV-1.2.