Search Results (29)

Background: Postnatal cytomegalovirus (pCMV) infection is a frequent viral condition in early infancy and is primarily acquired through maternal breastfeeding. Although usually asymptomatic in term infants, it can lead to significant morbidity in preterm neonates (gestational age < 32 weeks) and in those with very low birthweight (<1500 g), presenting with sepsis-like syndrome, pneumonia, cytopenia, hepatitis, or colitis. Severe cases may result in long-term sequelae or death. Objectives: To describe a series of cases of pCMV infection and review the current evidence on its epidemiology, clinical manifestations, outcomes, and therapeutic management, aiming to identify gaps in knowledge and propose opportunities for improving the care of preterm infants. Methods: We analyzed clinical presentations of pCMV disease in a case series of preterm infants and reported cases and reviewed the recent literature regarding diagnostic approaches, antiviral therapy, and strategies for breastmilk management. Results: Current data highlight substantial variability in clinical management and outcomes. The lack of consensus on antiviral indications and treatment duration reflects a limited understanding of the disease’s natural history. Approaches to breastmilk handling differ widely among centers and countries, further complicating the standardization of care. Conclusions: pCMV infection remains a relevant yet under-recognized condition in neonatal medicine. Improved diagnostic strategies, clearer therapeutic guidelines, and harmonized recommendations for breastmilk management are needed to optimize the care of preterm infants at risk of or affected by pCMV disease. Full article

Porcine cytomegalovirus, more accurately classified as porcine roseolovirus (PCMV/PRV), was shown to be pathogenic in the context of xenotransplantation. Transmission of PCMV/PRV to non-human primates receiving hearts or kidneys from virus-positive pigs significantly reduced the survival time of the recipients. PCMV/PRV was also transmitted to the first human recipient of a pig heart transplant and contributed to the patient’s death. Although PCMV/PRV is highly prevalent in all pig breeds and wild boars, including slaughterhouse pigs, no infections or diseases have been reported in healthy, ill, or immunocompromised humans, suggesting that this virus is not zoonotic and should therefore be classified as xenozoonotic. This indicates that this virus is not zoonotic and must be classified as xenozoonotic. Moreover, it remains unclear whether PCMV/PRV is capable of infecting human cells in vitro. To address this question, human 293T cells resistant to hygromycin were co-cultured with porcine fallopian tube (PFT) cells producing PCMV/PRV. After hygromycin selection, the remaining human cells showed no evidence of infection. Because herpesviruses are generally considered to be species-specific—a notion that has been shown to be not entirely correct—it was also investigated whether PCMV/PRV can infect mouse cells using the same approach. Similarly, no infection was observed. Since the target cells employed in both assays had a reduced capacity to resist viral infection, the findings strongly suggest that PCMV/PRV is unable to infect human or mouse cells, which are equipped with functional antiviral mechanisms. This is supported by findings from the patient who received the first pig heart transplantation. Full article

Xenotransplantation using pig cells, tissues, or organs is advancing toward clinical application to address the shortage of human donor organs for treating organ failure. However, this emerging technology carries the risk of transmitting pathogenic porcine microorganisms, particularly viruses. The recent transmission of a porcine herpesvirus to the first human recipient of a pig heart highlights the urgent need for more rigorous screening of donor pigs. To identify potentially pathogenic porcine viruses, highly sensitive and specific detection methods are required. PCR-based techniques able to detect porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), hepatitis E virus (HEV), porcine circoviruses (PCV1-4), porcine lymphotropic herpesviruses (PLHV-1-3), porcine endogenous retroviruses (PERVs), porcine parvovirus (PPV), Torque teno sus viruses (TTSuV1,2), atypical porcine pestivirus (APPV) and SARS-CoV-2 were established. Immunological assays that detect antibodies as indirect indicators of infection were established for PCMV/PRV, HEV, PLHVs and PERVs. Since most veterinary laboratories focus on detecting viruses that are pathogenic to pigs and cause economic losses to the swine industry, screening for viruses relevant to xenotransplantation should be conducted in specialized virological diagnostic units. In this context, we present a complete collection of the newest and detailed protocols for comprehensive viral screening, along with guidance on how to implement these methods effectively. Full article

Postnatal cytomegalovirus (pCMV) infection is typically asymptomatic in term infants but poses significant risks to very preterm and very low birth weight (VLBW) infants. The primary mode of transmission of pCMV is breast milk from seropositive mothers. Here, we present the case of a 29-week preterm female who contracted pCMV and began to manifest symptoms at day of life (DOL) 50. She developed respiratory compromise, massive ascites, and was extremely ill. The patient was managed with ganciclovir (GCV), intravenous immunoglobulins (IVIG), and percutaneous drainage of the ascites. She gradually improved and was discharged after a 5-month neonatal intensive care unit (NICU) stay. After presenting the case, we review the clinical manifestations of pCMV, and particularly its less well-recognized gastrointestinal manifestations, including ascites. We then outline guidelines for treatment and prevention. Clinicians should consider pCMV in VLBW and extremely premature infants presenting with thrombocytopenia, colitis, or ascites, especially in the second and third months of life. Full article

Porcine lymphotropic herpesviruses -1, -2, and -3 (PLHV-1, PLHV-2, and PLHV-3) are gammaherpesviruses that are widespread in pigs. These viruses are closely related to the human pathogens Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), both of which are known to cause severe diseases in humans. To date, however, no definitive association has been established between PLHVs and any disease in pigs. With the growing interest in xenotransplantation as a means to address the shortage of human organs for transplantation, the safety of using pig-derived cells, tissues, and organs is under intense investigation. In preclinical trials involving pig-to-nonhuman primate xenotransplantation, another porcine herpesvirus—porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV)—was shown to be transmissible and significantly reduced the survival time of the xenotransplants. In the present study, we examined donor pigs and their respective baboon recipients, all of which were part of preclinical pig heart xenotransplantation studies, for the presence of PLHV. PLHV-1, PLHV-2, and PLHV-3 were detected in nearly all donor pigs; however, no evidence of PLHV transmission to the baboon recipients was observed. Full article

Wild boars are recognized reservoirs of numerous viral pathogens, posing a significant risk to domestic pig populations, particularly in areas with poor biosecurity. This study assessed the prevalence and co-infection patterns of porcine circovirus type 2 (PCV2), porcine parvovirus (PPV), porcine cytomegalovirus (PCMV), African swine fever virus (ASFV), classical swine fever virus (CSFV), and pseudorabies virus (PRV) in wild boars from western Serbia and the Republic of Srpska (Bosnia and Herzegovina). Sixty-six spleen samples from legally hunted wild boars were analyzed by qPCR. All animals were negative for ASFV, CSFV, and PRV. The cumulative prevalence of infection with at least one of the other three viruses was 86.4% (95% CI: 76.2–92.8%). PCMV was detected in 74.2% of samples, PCV2 in 50%, and PPV in 28.8%. Co-infections were common: 42.4% of animals were positive for two viruses, and 12.1% for all three. A statistically significant association was observed between triple co-infection and sex, with higher rates in males. Subadult wild boars showed the highest PCV2 + PCMV co-infection rate (p = 0.0547). These findings highlight the need to expand molecular surveillance, particularly for PCMV, in both wild and domestic pigs, especially in regions reliant on low-biosecurity backyard farming. Full article

Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and higher production costs in the global pig industry. Our goal was to conduct a comprehensive study correlating both the anti-PRRSV immune response and 21 secondary infectious agents with PRDC severity. Methods: To this end, PRRSV-negative weaners were vaccinated with a PRRSV-2 MLV and put into a farm with a history of PRDC. Subsequently, anti-PRRSV cellular and antibody responses were monitored pre-vaccination, at 28 days post vaccination (dpv) and during PRDC outbreak (49 dpv). NanoString was used to quantify 21 pathogens within the bronchoalveolar lavage (BAL) at the time of necropsy (51 dpv). PRRSV-2 was present in 53 out of 55 pigs, and the other five pathogens (PCMV, PPIV, B. bronchiseptica, G. parasuis, and M. hyorhinis) were detected in BAL samples. Results: Although the uncontrolled settings of field trials complicated data interpretation, multivariate correlation analyses highlighted valuable lessons: (i) high weaning weight predicted animal resilience to disease and high weight gains correlated with the control of the PRRSV-2 field strain; (ii) most pigs cleared MLV strain within 7 weeks, and the field PRRSV-2 strain was the most prevalent lung pathogen during PRDC; (iii) all pigs developed a systemic PRRSV IgG antibody response which correlated with IgG and IgA levels in BAL; (iv) the induction of anti-field strain-neutralizing antibodies by MLV PRRSV-2 vaccination was both late and limited; (v) cellular immune responses were variable but included strong systemic IFN-γ production against the PRRSV-2 field strain; (vi) the most detected lung pathogens correlated with PRRSV-2 viremia or lung loads; (vii) within the six detected pathogens, two viruses, PRRSV-2 and PCMV, significantly correlated with the severity of the clinical outcome. Conclusions: While a simple and conclusive answer to the multifaceted nature of PRDC remains elusive, the key lessons derived from this unique study provide a valuable framework for future research on porcine respiratory diseases. Full article

Pigs are affected by a variety of pathogenic agents that need to be identified correctly and diagnosed even when co-infections may complicate the application of specific and targeted assays. Next-generation sequencing can provide new perspective to monitor viruses infecting or co-infecting diseased pigs. In this study, we tested, for the first time for diagnostic purposes in a livestock species, a new method based on whole-genome sequencing of all the DNAs extracted from the blood of nine pigs sampled from a farm where there was a suspected outbreak of Post-weaning Multisystemic Wasting Syndrome. We then used unmapped reads on the porcine reference genome to mine for viral sequences using a specifically designed bioinformatic pipeline. Within this fraction of reads, viral sequences ranged from 0.002% to 4.4% of the total unmapped reads and were derived from twelve different viruses known to infect pigs, where three were herpesviruses, eight were parvoviruses, and one was a circovirus. All pig sequencing datasets were positive for one or more viruses, with various potential viral loads. Suid betaherpesvirus 2, also known as Porcine cytomegalovirus (PCMV), was the most frequently identified virus as five out of the nine pig sequencing datasets contained viral sequences from this virus. The results may suggest a heterogeneous viral profile of the diseased pigs that may be derived from potential secondary infections or co-infections. This pilot application demonstrated that a whole-genome sequencing approach can complement other routine diagnostic assays in veterinary virology. Other studies and improvements are needed to validate the results and apply this approach in routine monitoring applications. Full article

Contrary to extensively studied porcine alphaherpesvirus (SuHV-1/PRV), betaherpesvirus (SuHV-2/PCMV) and Gammaherpesvirinae (SuHV-3/PLHV-1, SuHV-4/PLHV-2, SuHV-5/PLHV-3) infections remain unexplored in the swine population in Poland. The aim of this study was to characterise the prevalence of infections and local strains from each major herpesvirus subfamily on a large-scale weaner farm located in Poland. Nasal swabs collected from pigs at 6, 8 and 10 weeks of age were tested for the presence of herpesvirus infections using nested PCR specific to the pan-herpesvirus DNA polymerase (DPol) gene. The amplicons obtained from the positive samples were sequenced using the Sanger method. In total, 60% of the pigs were positive for herpesviruses, including 35.6% for porcine cytomegalovirus (SuHV-2/PCMV) and 24.4% for porcine lymphotropic herpesvirus type 1 (SuHV-3/PLHV-1). The infection rate was lowest in 6-week-old pigs—20% (6.7%—PCMV, 13.3%—PLHV-1) in comparison to 8-week-old—80% (53.3%—PCMV, 26.7% PLHV-1)—and 10-week-old pigs—80% (46.7%—PCMV, 33.3%—PLHV-1). No correlation between PCMV and PLHV-1 infections and coinfections with IAV, PRV1 or PRRSV was observed. Sequence analysis of both PLHV-1 and PCMV showed high genetic uniformity. Additionally, PLHV-1 isolates showed a close relationship to strains isolated from wild boar in Poland and pigs in Germany in recent years. In summary, our study confirmed the presence of both PLHV-1 and PCMV infections occurring early in piglet development, probably after passive immunity cessation. Full article

Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), a porcine herpesvirus, has been shown to significantly reduce the survival time of porcine xenotransplants in non-human primates. The virus was detected in all the examined organs of baboons transplanted with PCMV/PRV-positive organs and it was also transmitted to the first human recipient of a pig heart, contributing to the patient’s death. PCMV/PRV induces consumptive coagulopathy and thrombocytopenia in xenotransplant recipients. Initial studies in baboons revealed that the virus triggered increased release of tumor necrosis factor α (TNFα) and interleukin 6 (IL-6), along with elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) complexes. Since there is no evidence that PCMV/PRV infects primate cells, including human cells, the virus appears to directly interact with immune and endothelial cells, disrupting cytokine signaling and coagulation pathways. The highest viral load was detected in the explanted pig heart, suggesting active replication at this site. Additionally, cells expressing PCMV/PRV proteins were identified in all the examined baboon organs, where pig cells were also found. Since PCMV/PRV affects only xenotransplant recipients and not healthy humans, this condition should be classified as a xenozoonosis. Interestingly, antibodies against human herpesvirus 6 (HHV-6) cross-react with PCMV/PRV and may contribute to protection against infection in humans. Further research is needed to uncover the molecular mechanisms underlying this xenozoonotic disease. Full article

Detection methods have been developed to prevent transmission of zoonotic or xenozoonotic porcine viruses after transplantation of pig organs or cells to the recipient (xenotransplantation). Eleven xenotransplantation-relevant viruses, including porcine cytomegalovirus, porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses -1, -2, -3 (PLHV-1, 2, 3), porcine parvovirus (PPV), porcine circovirus 2, 3, 4 (PCV2, 3, 4), hepatitis E virus genotype 3 (HEV3), porcine endogenous retrovirus-C (PERV-C), and recombinant PERV-A/C have been selected. In the past, several pig breeds, minipigs, and genetically modified pigs generated for xenotransplantation had been analyzed using these methods. Here, spleen, liver, and blood samples from 10 German slaughterhouse pigs were screened using both PCR-based and immunological assays. Five viruses: PCMV/PRV, PLHV-1, PLHV-3, and PERV-C, were found in all animals, and PCV3 in one animal. Some animals were latently infected with PCMV/PRV, as only virus-specific antibodies were detected. Others were also PCR positive in the spleen and/or liver, indicative of an ongoing infection. These results provide important information on the viruses that infect German slaughterhouse pigs, and together with the results of previous studies, they reveal that the methods and test strategies efficiently work under field conditions. Full article

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation. Full article

Porcine cytomegalovirus (PCMV) infection is widespread worldwide and has a high prevalence in swine herds, especially in countries with intensive swine production. PCMV is zoonotic and can impact xenotransplants. It is the third swine virus known to be zoonotic, following swine influenza virus (influenza A) and hepatitis E virus genotype 3 (HEVgt3 or HEV-3). Wild boars, serving as reservoirs for various pathogens, including PCMV, pose a risk to both the pig industry and public health. This study aimed to investigate PCMV infection in Serbian wild boars using real-time PCR and assess other viral infections. We also tested samples for the presence of other viral infections: Aujeszky disease virus (ADV), Porcine parvovirus (PPV) and Porcine reproductive respiratory syndrome (PRRSV). Samples from 50 wild boars across 3 districts were tested. Results showed 8% positivity for PCMV DNA, with females showing higher infection rates. Porcine parvovirus (PPV) was detected in 56% of samples, while Porcine reproductive respiratory syndrome virus (PRRSV) was absent. ADV was found in 18% of samples, primarily in younger animals. This research contributes to understanding PCMV prevalence in Serbian wild boars and emphasizes the importance of monitoring viral infections in wild populations, considering the potential zoonotic and economic implications. Full article

Tibetan pig is a unique pig breed native to the Qinghai–Tibet Plateau. To investigate viral communities associated with porcine respiratory disease complex (PRDC), 167 respiratory samples were collected from Tibetan pigs in the Ganzi Tibetan autonomous prefecture of Sichuan province. Following library construction and Illunima Novaseq sequencing, 18 distinct viruses belonging to 15 viral taxonomic families were identified in Tibetan pigs with PRDC. Among the 18 detected viruses, 3 viruses were associated with PRDC, including porcine circovirus type 2 (PCV-2), Torque teno sus virus (TTSuV), and porcine cytomegalovirus (PCMV). The genomic sequences of two PCV-2 strains, three TTSuV strains, and one novel Porprismacovirus strain were assembled by SOAPdenovo software (v2). Sequence alignment and phylogenetic analysis showed that both PCV-2 strains belonged to PCV-2d, three TTSuVs were classified to TTSuV2a and TTSuV2b genotypes, and the Porprismacovirus strain PPMV-SCgz-2022 showed a close genetic relationship with a virus of human origin. Recombination analysis indicated that PPMV-SCgz-2022 may have originated from recombination events between Human 16,806 × 66-213 strain and Porcine 17,668 × 82-593 strain. Furthermore, the high proportion of single infection or co-infection of PCV2/TTSuV2 provides insight into PRDC infection in Tibetan pigs. This is the first report of the viral communities in PRDC-affected Tibetan pigs in this region, and the results provides reference for the prevention and control of respiratory diseases in these animals. Full article

In the world’s first pig-to-human cardiac cytomegalovirus (PCMV), xenotransplant and elevated levels of porcine key factors contributing to patient mortality were considered. This has renewed attention on PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effectively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infection capabilities. This opens up possibilities for the future production of pig populations with antiviral functionalities. Full article