Abortion Storms Research Articles

First report on whole genome sequencing and comparative genomics of Salmonella enterica serovar Abortusequi isolated from Donkey in India.

Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi) is a leading cause of abortion in equines that hinders the rapid growth of equine industry. S. Abortusequi infection in equids has re-emerged over last ten years. In the present study, S. Abortusequi was isolated and characterized from donkeys during an abortion storm in the southern peninsular region of India. Further, whole genome sequencing and phylogenomic analysis revealed that the present isolate was clustered among S. Abortusequi clade. The core genome MLST (cgMLST) analysis based on hierarchical clustering and single nucleotide polymorphism (SNP) core-genome dendrogram of the present isolate against 10S. Abortusequi isolates revealed that the present isolate established a distinct clade compared to all previously reported isolates. A comparison of cgMLST and SNP analyses revealed the same clustering concordance between isolates. In addition, comparative genomics and phylogenetic analysis was carried out with six S. Abortusequi serovars showed a higher number of core genes than accessory genes. Further, comparative analysis of phenotype and genotype antimicrobial resistance revealed a concordance of 32% and discordance of 68% respectively.

Development of a live attenuated vaccine candidate for equid alphaherpesvirus 1 control: a step towards efficient protection.

Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as a molecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and ΔUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the ΔgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the ΔUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the ΔUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection.

Public health importance of brucellosis: a review

Members of the genus Brucella are the source of the infectious bacterial disease known as brucellosis which is characterised by abortion, retained fetal membranes, orchitis, infection of the male accessory sex glands, and decreased fertility. Cattle, pigs, goats, sheep, dogs, camels, and occasionally horses are the animals most commonly affected by the disease. It affects sexually mature animals and its preferred site is the reproductive tract of both male and female animals. Animals may acquire the infection by licking the genitalia of infected female animals shortly after parturition or abortion, or by consuming contaminated pastures, feedstuffs, and water. Because there are insufficient domestic animal health programs, adequate diagnostic facilities, and effective public health measures, brucellosis is common and seen as an important public health concern in developing countries. Due to its association with abortion storm in newly infected herds, a high rate of retained placenta, endometritis or metritis which lowers milk production, and infertility, the disease is important economically. Additionally, the contagious nature of the disease has an impact on public health. In humans, brucellosis is an acute or subacute condition that can last for weeks or months. It is typically characterized by an intermittent or remittent fever, malaise, anorexia, and prostration. Humans can become infected by consuming contaminated animal products such as milk. These and control strategies of brucellosis that include good farm management practices, surveillance, culling of infected animals, use of proper vaccination protocols and public awareness were the subject matter of this review.

Public health importance of brucellosis: a review

Members of the genus Brucella are the source of the infectious bacterial disease known as brucellosis which is characterised by abortion, retained fetal membranes, orchitis, infection of the male accessory sex glands, and decreased fertility. Cattle, pigs, goats, sheep, dogs, camels, and occasionally horses are the animals most commonly affected by the disease. It affects sexually mature animals and its preferred site is the reproductive tract of both male and female animals. Animals may acquire the infection by licking the genitalia of infected female animals shortly after parturition or abortion, or by consuming contaminated pastures, feedstuffs, and water. Because there are insufficient domestic animal health programs, adequate diagnostic facilities, and effective public health measures, brucellosis is common and seen as an important public health concern in developing countries. Due to its association with abortion storm in newly infected herds, a high rate of retained placenta, endometritis or metritis which lowers milk production, and infertility, the disease is important economically. Additionally, the contagious nature of the disease has an impact on public health. In humans, brucellosis is an acute or subacute condition that can last for weeks or months. It is typically characterized by an intermittent or remittent fever, malaise, anorexia, and prostration. Humans can become infected by consuming contaminated animal products such as milk. These and control strategies of brucellosis that include good farm management practices, surveillance, culling of infected animals, use of proper vaccination protocols and public awareness were the subject matter of this review.

Salmonella Montevideo responsible for an abortion storm in housed ewes.

Salmonella Montevideo responsible for an abortion storm in housed ewes.

Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies.

Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT provide the first line of defense against EHV-1 and are crucial for orchestrating immunity. To define host-pathogen interactions, we characterized B-cell responses, antibody isotype functions, and EHV-1 replication of susceptible (non-immune) and clinically protected (immune) horses after experimental EHV-1 infection. Nasal secretion and nasal wash samples were collected and used for the isolation of DNA, RNA, and mucosal antibodies. Shedding of infectious virus, EHV-1 copy numbers, viral RNA expression, and host B-cell activation in the URT were compared based on host immune status. Mucosal EHV-1-specific antibody responses were associated with EHV-1 shedding and viral RNA transcription. Finally, mucosal immunoglobulin G (IgG) and IgA isotypes were purified and tested for neutralizing capabilities. IgG1 and IgG4/7 neutralized EHV-1, while IgG3/5, IgG6, and IgA did not. Immune horses secreted high amounts of mucosal EHV-1-specific IgG4/7 antibodies and quickly upregulated B-cell pathway genes, while EHV-1 was undetected by virus isolation and PCR. RNA transcription analysis reinforced incomplete viral replication in immune horses. In contrast, complete viral replication with high viral copy numbers and shedding of infectious viruses was characteristic for non-immune horses, together with low or absent EHV-1-specific neutralizing antibodies during viral replication. These data confirm that pre-existing mucosal IgG1 and IgG4/7 and rapid B-cell activation upon EHV-1 infection are essential for virus neutralization, regulation of viral replication, and mucosal immunity against EHV-1.IMPORTANCEEquine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion storms, and neurologic outbreaks known as equine herpes myeloencephalopathy (EHM). EHV-1 is transmitted with respiratory secretions by nose-to-nose contact or via fomites. The virus initially infects the epithelium of the upper respiratory tract (URT). Host-pathogen interactions and mucosal immunity at the viral entry site provide the first line of defense against the EHV-1. Robust mucosal immunity can be essential in protecting against EHV-1 and to reduce EHM outbreaks. It has previously been shown that immune horses do not establish cell-associated viremia, the prerequisite for EHM. Here, we demonstrate how mucosal antibodies can prevent the replication of EHV-1 at the epithelium of the URT and, thereby, the progression of the virus to the peripheral blood. The findings improve the mechanistic understanding of mucosal immunity against EHV-1 and can support the development of enhanced diagnostic tools, vaccines against EHM, and the management of EHV-1 outbreaks.

HSP90 is part of a protein complex with the L polymerase of Rift Valley fever phlebovirus and prevents its degradation by the proteasome during the viral genome replication/transcription stage.

The mosquito-borne Rift Valley fever virus (RVFV) from the Phenuiviridae family is a single-stranded RNA virus that causes the re-emerging zoonotic disease Rift Valley fever (RVF). Classified as a Category A agent by the NIH, RVFV infection can cause debilitating disease or death in humans and lead to devastating economic impacts by causing abortion storms in pregnant cattle. In a previous study, we showed that the host chaperone protein HSP90 is an RVFV-associated host factor that plays a critical role post viral entry, during the active phase of viral genome replication/transcription. In this study, we have elucidated the molecular mechanisms behind the regulatory effect of HSP90 during infection with RVFV. Our results demonstrate that during the early infection phase, host HSP90 associates with the viral RNA-dependent RNA polymerase (L protein) and prevents its degradation through the proteasome, resulting in increased viral replication.

CK1 and PP1 regulate Rift Valley fever virus genome replication through L protein phosphorylation

Rift Valley fever virus (RVFV) is an arbovirus in the Phenuiviridae family identified initially by the large ‘abortion storms’ observed among ruminants; RVFV can also infect humans. In humans, there is a wide variation of clinical symptoms ranging from subclinical to mild febrile illness to hepatitis, retinitis, delayed-onset encephalitis, or even hemorrhagic fever. The RVFV is a tri-segmented negative-sense RNA virus consisting of S, M, and L segments. The L segment encodes the RNA-dependent RNA polymerase (RdRp), termed the L protein, which is responsible for both viral mRNA synthesis and genome replication. Phosphorylation of viral RdRps is known to regulate viral replication. This study shows that RVFV L protein is serine phosphorylated and identified Casein Kinase 1 alpha (CK1α) and protein phosphatase 1 alpha (PP1α) as L protein binding partners. Inhibition of CK1 and PP1 through small molecule inhibitor treatment, D4476 and 1E7-03, respectively, caused a change in the phosphorylated status of the L protein. Inhibition of PP1α resulted in increased L protein phosphorylation whereas inhibition of CK1α decreased L protein phosphorylation. It was also found that in RVFV infected cells, PP1α localized to the cytoplasmic compartment. Treatment of RVFV infected cells with CK1 inhibitors reduced virus production in both mammalian and mosquito cells. Lastly, inhibition of either CK1 or PP1 reduced viral genomic RNA levels. These data indicate that L protein is phosphorylated and that CK1 and PP1 play a crucial role in regulating the L protein phosphorylation cycle, which is critical to viral RNA production and viral replication.

In silico identification of novel pre-microRNA genes in Rift valley fever virus suggest new pathomechanisms for embryo-fetal dysgenesis

ABSTRACT MicroRNAs (miRNAs) are small non-coding RNAs that regulate the post-transcriptional expression of target genes. Virus-encoded miRNAs play an important role in the replication of viruses, modulate gene expression in both the virus and host, and affect their persistence and immune evasion in hosts. This renders viral miRNAs as potential targets for therapeutic applications, especially against pathogenic viruses that infect humans and animals. Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic RNA virus that causes severe disease in both humans and livestock. High mortality among newborn lambs and abortion storms are key characteristics of an RVF outbreak. To date, limited information is available on RVFV-derived miRNAs. In this study, computational methods were used to analyse the RVFV genome for putative pre-miRNA genes, which were then analysed for the presence of mature miRNAs. We detected 19 RVFV-encoded miRNAs and identified their potential mRNAs targets in sheep (Ovis aries), the most susceptible host. The identification of significantly enriched O. aries genes in association with RVFV miRNAs will help elucidate the molecular mechanisms underlying RVFV pathogenesis and potentially uncover novel drug targets for RVFV.

Longitudinal surveillance of Coxiella burnetii following an abortion storm in domestic goats.

Q fever is a disease caused by Coxiella burnetii, which can cause serious illness in humans and abortions in goats. A Q fever outbreak among an unvaccinated goat herd led to a 65% loss of the kid crop in spring 2018. To assess the impact of the outbreak on the herd and environment, longitudinal surveillance of the ranch was conducted across three samplings in September 2018, April 2019, and May 2022. Antibodies against C. burnetii were monitored by an indirect immunofluorescence assay. Shedding was monitored through analysis of vaginal/fecal swabs and milk. Environmental swabs and bulk soil were collected from various locations around the ranch. Animal and environmental samples were analyzed for C. burnetii DNA by PCR. Herd-level seroprevalence decreased from 89% in 2018 to 84.3% in 2019, and 64.5% in 2022. Overall herd shedding was 14.4% in 2018, 7.4% in 2019, and 6.7% in 2022. The percentage of C. burnetii-positive environmental samples was 83.7% in 2018, 51.7% in 2019, and 28.6% in 2022. Serological evidence suggests that new infections were occurring in the herd 4 years post-abortion storm. This study demonstrates the presence of C. burnetii shedding and environmental contamination in a goat operation at least four kidding seasons after an outbreak. A better understanding of management practices that can improve outcomes for infected herds, particularly in areas without access to vaccines against C. burnetii, is needed to better protect operators and the public.

A Retrospective Investigation of Abortion Storm in Abergele Goats, Waghimira Zone, Amhara Region, Ethiopia.

A retrospective study was conducted in Abergele and Ziquala districts in Ethiopia to investigate the occurrence, impact, and potential risk factors for abortion in small ruminants linked to a regional abortion storm. Affected (case) and nonaffected (control) villages were compared to assess infectious and noninfectious risk factors causing abortions. A case village was defined as a village with abortion seen in all households enrolled in the study, while a control village is characterized by presence of abortion in two and fewer households. A questionnaire survey, focus group discussions, and serological examinations were used to assess the differences in the abortion rate between the case and control villages. The Rose Bengal Plate Test for Brucellosis, Toxoplasma gondii Antibody Test Kit for Toxoplasma gondii, and ELISA for Chlamydophila abortus and Coxiella burnetii were used to detect antibodies. Per village 15 household flocks were selected. In the case villages, all flocks were affected by abortion (a mean abortion of 13 animals in Abergele and 9 in Ziquala). In contrast, only three households reported abortions in the control villages. A total of 176 blood samples were collected from the case and control villages for further laboratory diagnosis of possible causes of abortion. Of the examined flocks, 17%, 10.2%, and 2.8% were positive for Coxiella burnetii, Toxoplasma gondii, and Chlamydophila abortus, respectively. However, antibodies against Brucella melitensis were not detected. While the seroprevalence was greater for some infectious agents of abortion, there was no significant difference between the case and control villages. It is clear that the abortion problem in the study villages is complex and likely due to a mix of poor husbandry practices and the presence of infectious diseases. To better understand the underlying causes of abortion, there is a need to conduct a longitudinal study involving testing for more pathogens at the household level combined with reliable data on husbandry practices.

An abortion storm in a goat farm in the Northeast Region of Brazil was caused by the atypical Toxoplasma gondii genotype #13

The objective of this study was to characterise a Toxoplasma gondii-induced abortion outbreak on a goat farm in the State of Paraíba, Northeast Region of Brazil. From a herd of 10 does, seven experienced abortions and one gave birth to twins (one stillborn and the other weak and underdeveloped). Serum samples from all of the does were analysed by indirect fluorescent antibody test (IFAT). Samples of colostrum and placenta from two does, along with lung, heart, brain and umbilical cord samples from four of the foetuses, were screened by nested ITS1 PCR specific for T. gondii. The positive samples were then analysed by multiplex nested PCR-RFLP. All ten does tested positive by IFAT for anti-T. gondii IgG (titrations ranging from 1:4096 to 1:65,536). The ITS1 PCR screening revealed T. gondii DNA in the placenta (2/2), colostrum (2/2), umbilical cord (2/4), lung (1/4), heart (1/4), and brain (1/4). Four samples produced complete RFLP genotyping results, identifying a single genotype, ToxoDB #13. In conclusion, we demonstrated a high rate of abortion caused by T. gondii in a goat herd, highlighting the pathogenicity of genotype #13, one of the most prevalent genotypes of T. gondii in Brazil.

Abortion storm of Yili horses is associated with Equus caballus papillomavirus 2 variant infection.

Nine different species of Equus caballus papillomavirus (EcPV) and three bovine papillomaviruses (BPVs) have been reported to infect horses. However, there are few descriptions of such infections in China. In our pioneer study on Chinese horses, we identified EcPV-2 in the nasal swabs (4/230, 1.7%) of Yili horses, and the semen (3/18, 16.7%) of thoroughbred horses. This indicated that EcPV is indeed hosted by horses in China, and that EcPV-2 might be transmitted though breeding. Further detection of EcPVs in the lung tissues of aborted fetuses of Yili horses, which were originally negative for equid herpes viruses, demonstrated EcPV-2 positivity in 19 of 50 samples, thereby indicating that EcPV-2 may be a new pathogen responsible for causing abortion. Thereafter, sequence analyses of the L1 genes of 26 EcPV-2 in China were performed, indicating that EcPV-2, which primarily infects horses in China, shared 98.3-99.9% nt identity with the published sequences for EcPV-2. These observations indicated that EcPV-2 identified in the current study were highly similar variants of the previously identified strains of EcPV-2. Phylogenetic analysis based on L1 gene sequences from GenBank showed that the EcPV-2 found in Chinese horses was closely related to and clustered together with an already known EcPV-2a lineage. Our study provides the first evidence related to EcPV-2 infection in Chinese horses, which can serve as a causative agent for Yili horse abortions, and may thus lay the foundation for a systematic and detailed epidemiological study of this infection in Chinese horses.

New insights into phenotype and genotype relationships in Neospora caninum.

The successful isolation of four new Neospora caninum strains from different regions and with different backgrounds (obtained from an abortion storm or congenitally infected and asymptomatic calves) allowed us previously to characterize natural isolates, finding differences in phenotype and microsatellites. Given the variability observed, we wondered in this work whether these differences had consequences in virulence, invasion and vertical transmission using cell cultures and murine neosporosis models. In addition, we performed the genomic analysis and SNP comparative studies of the NcURU isolates. The results obtained in this work allowed us to establish that NcURU isolates are of low virulence and have unique phenotypic characteristics. Likewise, sequencing their genomes has allowed us to delve into the genetic singularities underlying these phenotypes, as well as the common mutated genes. This work opens a new perspective for diagnostic purposes and formulating possible vaccines based on attenuated strains.

11 Impact of a Cache Valley Fever Outbreak on Lambing Performance in a Landrace Hair Sheep Flock: A Case Study

Abstract Cache Valley Fever (CVF) is a mosquito-born, viral disease endemic to North America. While generally not associated with clinical symptoms in ewes, it affects fetal development during the first trimester of pregnancy resulting in malformations and pregnancy loss. A suspected outbreak of CVF was recorded in a flock of Barbados Blackbelly and St. Croix hair sheep managed under an 8-mo, accelerated mating system with ewes bred in March, July and November. The outbreak was associated with a July breeding, in a summer with unusually high rainfall and standing water in pastures. There had been no previous occurrence of CVF or other abortion storms in the flock (20+ years). Lambing outcome associated with the suspected outbreak of CVF was compared with that of the three prior July matings (CON). Ewes (n = 32-35) were managed in a pasture-based system under rotational grazing. Ewes were mated in two single sire groups of 16 to 18 ewes to like-breed sires each breeding season. Pregnancy was determined by transrectal ultrasound at end and 21 d after the 25-day breeding season. Ewes lambed on pasture, and lambs were tagged, and birth weights recorded within 24 hours. Blood samples were collected from all ewes following the CVF lambing and submitted for CVF antibody testing. All ewes showed CVF antibody titers. Pregnancy rate for the CVF lambing was not different from CON (85.7 vs. 89.8%; P = 0.512), whereas lambing rate was less in CVF for both ewes exposed (74.3 vs. 88.8%; P = 0.039) and ewes lambing (86.7 vs. 98.9%; P = 0.004). Incidence of stillborn and neonatal death of lambs was greater in CVF than CON (37.0 vs.5.6%; P = 0.002), as was the number of malformed lambs (13.0 vs. 0%; P < 0.001). Malformed lambs were associated with breech presentations. Litter size was not different in the CVF lambing (1.77 vs 1.86; P = 0.471), but lamb birth weight tended to be less (2.80 vs. 3.04 kg; P = 0.055) while ewe postpartum weight was not different (45.3 vs. 47.0 kg; P = 0.384). The outbreak of CVF reduced the lambing rate and increased the incidence of neonatal death and malformations. The outbreak occurred during a summer with unusually high rainfall and may be associated with changing weather patterns linked to climate change. Delaying summer breeding may be considered a mitigation strategy if feasible.

Bovine abortion storm highlights risk posed by Neospora-naive dogs.

Veterinary RecordVolume 192, Issue 6 p. 245-247 Surveillance Bovine abortion storm highlights risk posed by Neospora-naive dogs First published: 17 March 2023 https://doi.org/10.1002/vetr.2860Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume192, Issue618/25 March 2023Pages 245-247 RelatedInformation

Experimental Infection of Domestic Pigs (Sus scrofa) with Rift Valley Fever Virus.

Rift valley fever (RVF), caused by the RVF virus (RVFV), is a vector-borne zoonotic disease that primarily affects domestic ruminants. Abortion storms and neonatal deaths characterise the disease in animals. Humans develop flu-like symptoms, which can progress to severe disease. The susceptibility of domestic pigs (Sus scrofa domesticus) to RVFV remains unresolved due to conflicting experimental infection results. To address this, we infected two groups of pregnant sows, neonates and weaners, each with a different RVFV isolate, and a third group of weaners with a mixture of the two viruses. Serum, blood and oral, nasal and rectal swabs were collected periodically, and two neonates and a weaner from group 1 and 2 euthanised from 2 days post infection (DPI), with necropsy and histopathology specimens collected. Sera and organ pools, blood and oronasorectal swabs were tested for RVFV antibodies and RNA. Results confirmed that pigs can be experimentally infected with RVFV, although subclinically, and that pregnant sows can abort following infection. Presence of viral RNA in oronasorectal swab pools on 28 DPI suggest that pigs may shed RVFV for at least one month. It is concluded that precautions should be applied when handling pig body fluids and carcasses during RVF outbreaks.

Double and quadruple deletion mutant of EHV-1 is highly attenuated and induces optimal immune response

Equid alphaherpesvirus 1 (EHV-1) infection causes significant health problems in equines. The EHV-1 infection leads to abortion storm in mares, respiratory disease and myeloencephalopathy. Despite the wide use of vaccines, the outbreaks of EHV-1 infections keep occurring globally, suggesting the need for the development of improved vaccines. Gene deletion attenuated mutant viruses could be a good candidate for the development of modified live vaccines. Here, we report the generation of mutant EHV-1 by deleting virulence (glycoprotein E & internal repeat 6; IR6) and immune evasive (pUL43 & pUL56) associated genes either individually or in combinations; and comprehensive evaluation of mutants through in vitro characterization followed by in vivo study in murine model to adjudge the attenuation of the virus and immune responses generated by mutants vis-à-vis wild type (wt) virus. The EHV-1 mutants with deletion of IR6 and gE genes (vToH-DMV) and four genes (i.e., gE, IR6, pUL43 and pUL56) (vToH-QMV) revealed a significant reduction in plaque size with minimal loss in replication efficiency in comparison to the wt virus. Further, in vivo studies showed virus attenuation adjudged through significant reduction in clinical signs, weight loss, gross and histopathological lesions in comparison to wt virus also revealed improved immune responses estimated through serum neutralization and flow cytometric analysis of CD4 + and CD8 + cell populations. Thus it can be concluded that EHV-1 mutants viz. vToH-DMV and vToH-QMV (novel combination) are promising vaccine candidates and qualify to be studied for adjudging the protective efficacy with wt virus challenge.

Rift Valley Fever Virus Non-Structural Protein S Is Associated with Nuclear Translocation of Active Caspase-3 and Inclusion Body Formation.

Rift Valley fever phlebovirus (RVFV) causes Rift Valley fever (RVF), an emerging zoonotic disease that causes abortion storms and high mortality rates in young ruminants as well as severe or even lethal complications in a subset of human patients. This study investigates the pathomechanism of intranuclear inclusion body formation in severe RVF in a mouse model. Liver samples from immunocompetent mice infected with virulent RVFV 35/74, and immunodeficient knockout mice that lack interferon type I receptor expression and were infected with attenuated RVFV MP12 were compared to livers from uninfected controls using histopathology and immunohistochemistry for RVFV nucleoprotein, non-structural protein S (NSs) and pro-apoptotic active caspase-3. Histopathology of the livers showed virus-induced, severe hepatic necrosis in both mouse strains. However, immunohistochemistry and immunofluorescence revealed eosinophilic, comma-shaped, intranuclear inclusions and an intranuclear (co-)localization of RVFV NSs and active caspase-3 only in 35/74-infected immunocompetent mice, but not in MP12-infected immunodeficient mice. These results suggest that intranuclear accumulation of RVFV 35/74 NSs is involved in nuclear translocation of active caspase-3, and that nuclear NSs and active caspase-3 are involved in the formation of the light microscopically visible inclusion bodies.

Complete Genome Sequence of Brucella abortus 2308, Isolated from an Abortion Storm on a Dairy Farm in India.

The present report communicates the first complete genome sequence of Brucella abortus strain 2308, isolated from an abortion storm on a dairy farm in India. Bacteria were isolated in pure culture from the placentas of aborted calves, and next-generation sequencing (NGS) revealed that the genome sequence length of the isolated strain is 3,285,606 bp, with a GC content of 57.25%, an N50 value of 296,426 bp, and an L50 value of 4, containing 3,119 coding DNA sequences (CDSs), 49 tRNAs, 1 transfer-messenger RNA (tmRNA), and 3 rRNA genes.