Immunohistochemical Study of Stellate Cells in Patients with Chronic Viral Heptitis C Histopathological study

Background: Chronic hepatitis is defined as liver inflammation that lasts for at least 6 months. The Hepatitis C virus is responsible for 60 to 70% of chronic hepatitis cases; the virus causes continued inflammation that slowly damages the liver, eventually leading to cirrhosis, liver failure, and, in rare cases, liver cancer. Aim of the work: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, in patients with HCV chronic hepatitis. Material and methods: 50 hepatic core biopsies selected randomly were received from Histopathology Department at National Hepatology and Tropical Medicine Research Institute and examined for histopathological features using (hematoxylin and eosin), stage of hepatic fibrosis using stellate cell Masson s' trichrome stain, and examined for stellate cell activity using alpha smooth muscle actin (ASMA) immunostaining. Results: The relation between degree of ASMA expression by stellate cells and stage of fibrosis was highly significant with a p value <0.001, also the relation between degree of necroinflammation and degree of ASMA expression by stellate cells was highly significant with a p value <0.001. The relation between degree of necroinflammation and stage of fibrosis was highly significant with a p value <0.001. The relation between age of patient and stage of fibrosis also was statistically significant with a p value =0.012. The relation between age of patient and degree of necroinflammation was statistically significant with a p value =0.017. Conclusion: To summarize from hepatic core biopsies of patients suffering from chronic HCV, the number of active stellate cells was found to be positively associated with stage of hepatic fibrosis

SARS-CoV-2 infection of Chinese hamsters (Cricetulus griseus) reproduces COVID-19 pneumonia in a well-established small animal model

The SARS-CoV-2 pandemic has caused a yet unresolved global crisis. Effective medical intervention by vaccination or therapy seems to be the only possibility to control the pandemic. In this context, animal models are an indispensable tool for basic and applied research to combat SARS-CoV-2 infection. Here, we established a SARS-CoV-2 infection model in Chinese hamsters suitable for studying pathogenesis of the disease as well as pre-clinical testing of vaccines and therapies. This species of hamster is susceptible to SARS-CoV-2 infection as demonstrated by robust virus replication in the upper and lower respiratory tract accompanied by bronchitis and pneumonia as well as significant body weight loss following infection. The Chinese hamster features advantages compared to the Syrian hamster model, including more pronounced clinical symptoms, its small size, well-characterized genome, transcriptome and translatome data and availability of molecular tools

Current surveillance practices for shedding of elephant endotheliotropic herpesviruses in breeding and bachelor Asian elephant Elephas maximus herds in Europe

Elephant endotheliotropic herpesvirus-haemorrhagic disease (EEHV-HD) is the most common cause of death in juvenile captive Asian elephants Elephas maximus. Currently, weekly whole blood screening is recommended for the detection of viraemia, which occurs prior to the development of clinical disease, but there are no recommendations for monitoring viral shedding into the environment. The aims of this study were to evaluate current EEHV shedding surveillance protocols in Asian elephant herds in Europe, as well as to collate and describe existing EEHV shedding data from these herds. Results from a European Association of Zoos and Aquaria Taxon Advisory Group-approved survey revealed that as of January 2021, 42% of breeding institutions had a protocol for screening for EEHV viraemia, while 30% monitored viral shedding. Shedding data were available from 12 institutions, where a total of 2,863 samples had been collected for polymerase chain reaction (PCR) analysis. Overall, 13.9% of all tested samples were positive for EEHV and 48.9% of elephants tested positive for EEHV. EEHV-1 was both the most common genotype detected and the most commonly tested for. Evidence of the presence of EEHV was reported in 12/12 (100%) of breeding herds. Routine monitoring of EEHV shedding is recommended to enable better understanding of the dynamics of EEHV infection and disease

Genetic Diversity, Latency and Co-Infections

Alphaherpesviruses are highly prevalent in equine populations and co- infections with more than one of these viruses’ strains frequently diagnosed. Lytic replication and latency with subsequent reactivation, along with new episodes of disease, can be influenced by genetic diversity generated by spontaneous mutation and recombination. Latency enhances virus survival by providing an epidemiological strategy for long-term maintenance of divergent strains in animal populations. The alphaherpesviruses equine herpesvirus 1 (EHV-1) and 9 (EHV-9) have recently been shown to cross species barriers, including a recombinant EHV-1 observed in fatal infections of a polar bear and Asian rhinoceros. Little is known about the latency and genetic diversity of EHV-1 and EHV-9, especially among zoo and wild equids. Here, we report evidence of limited genetic diversity in EHV-9 in zebras, whereas there is substantial genetic variability in EHV-1. We demonstrate that zebras can be lytically and latently infected with both viruses concurrently. Such a co- occurrence of infection in zebras suggests that even relatively slow-evolving viruses such as equine herpesviruses have the potential to diversify rapidly by recombination. This has potential consequences for the diagnosis of these viruses and their management in wild and captive equid populations. View Full- Tex

The Roborovski Dwarf Hamster Is A Highly Susceptible Model for a Rapid and Fatal Course of SARS-CoV-2 Infection

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated an unprecedented and yet-unresolved health crisis worldwide. Different mammals are susceptible to SARS-CoV-2; however, few species examined so far develop robust clinical disease that mirrors severe human cases or allows testing of vaccines and drugs under conditions of severe disease. Here, we compare the susceptibilities of three dwarf hamster species (Phodopus spp.) to SARS-CoV-2 and introduce the Roborovski dwarf hamster (P. roborovskii) as a highly susceptible COVID-19 model with consistent and fulminant clinical signs. Particularly, only this species shows SARS-CoV-2-induced severe acute diffuse alveolar damage and hyaline microthrombi in the lungs, changes described in patients who succumbed to the infection but not reproduced in any experimentally infected animal. Based on our findings, we propose the Roborovski dwarf hamster as a valuable model to examine the efficacy and safety of vaccine candidates and therapeutics, particularly for use in highly susceptible individuals

Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters

In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals. Since age-dependent differences of COVID-19 were identified in humans, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)

An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission

Detection of equid herpesviruses among different Arabian horse populations in Egypt

Equid herpesviruses (EHVs) threaten equine health and can cause significant economic losses to the equine industry worldwide. Different equid herpesviruses, EHV‐1, EHV‐2, EHV‐4 and EHV5 are regularly detected among horse populations. In Egypt, monitoring is sporadic but EHV‐1 or EHV‐4 have been reported to circulate in the horse population. However, there is a lack of reports related to infection and health status of horses, likely due to the absence of regular diagnostic procedures. In the current study, the circulation of four infectious equid herpesviruses (EHV‐1, EHV‐2, EHV‐4 and EHV‐5) among different Arabian horse populations and donkeys residing the same farm was monitored. Different samples were collected and DNA was extracted and subjected to quantitative (q)‐PCR to detect the four equid herpesviruses using specific primers and probes. Antibody titres against EHV‐1 and EHV‐4 were tested using virus neutralization test and type‐specific ELISA. The results showed that EHV‐1, EHV‐2, EHV‐4 and EHV‐5 are endemic and can be a continuous threat for horses in the absence of vaccination programs and frequent virus reactivation. There is an urgent need for introduction of active regular surveillance measures to investigate the presence of different equid herpesviruses, and other equine viral pathogens, in various horse populations around Egypt and to establish a standardized cataloguing of equine health status

Comprehensive Serology Based on a Peptide ELISA to Assess the Prevalence of Closely Related Equine Herpesviruses in Zoo and Wild Animals

Equine herpesvirus type 1 (EHV-1) causes respiratory disorders and abortion in equids while EHV-1 regularly causes equine herpesvirus myeloencephalopathy (EHM), a stroke-like syndrome following endothelial cell infection in horses. Both EHV-1 and EHV-9 infections of non-definitive hosts often result in neuronal infection and high case fatality rates. Hence, EHV-1 and EHV-9 are somewhat unusual herpesviruses and lack strict host specificity, and the true extent of their host ranges have remained unclear. In order to determine the seroprevalence of EHV-1 and EHV-9, a sensitive and specific peptide-based ELISA was developed and applied to 428 sera from captive and wild animals representing 30 species in 12 families and five orders. Members of the Equidae, Rhinocerotidae and Bovidae were serologically positive for EHV-1 and EHV-9. The prevalence of EHV-1 in the sampled wild zebra populations was significantly higher than in zoos suggesting captivity may reduce exposure to EHV-1. Furthermore, the seroprevalence for EHV-1 was significantly higher than for EHV-9 in zebras. In contrast, EHV-9 antibody prevalence was high in captive and wild African rhinoceros species suggesting that they may serve as a reservoir or natural host for EHV-9. Thus, EHV-1 and EHV-9 have a broad host range favoring African herbivores and may have acquired novel natural hosts in ecosystems where wild equids are common and are in close contact with other perissodactyls