RESUMEN

There is a pressing need for effective feral cat management globally due to overabundant feline populations, disease transmission and their destructive impact on biodiversity. Virus-vectored immunocontraception (VVIC) is an attractive method for cat population management. Virus-vectored immunocontraceptives could be self-disseminating through horizontal transmission of the VVIC in feral cat populations, or they may be modified to act as non-transmissible vaccine-type immunocontraceptives for delivery to individual cats. These later constructs may be particularly attractive for use in owned (pet) cats and stray cats but could also be used for feral cats that are caught, vaccinated, and released. Here, we report the construction of three felid alphaherpesvirus 1 (FHV-1) derived immunocontraceptive candidates containing genes that encode for feline zona pellucida subunit 3 (ZP3) and gonadotropin-releasing hormone (GnRH). Two of the vaccine candidates were engineered to include disruptions to the thymidine kinase viral virulence gene to reduce the ability of the vaccines to be horizontally transmitted. Analysis of in vitro growth characteristics and protein expression are reported, and their potential for use as a population management tool for cats is discussed.

Asunto(s)

Anticoncepción Inmunológica , Animales , Gatos , Anticoncepción Inmunológica/métodos , Hormona Liberadora de Gonadotropina/inmunología , Vectores Genéticos/inmunología , Alphaherpesvirinae/inmunología , Alphaherpesvirinae/genética , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/inmunología , Varicellovirus/inmunología , Varicellovirus/genética

RESUMEN

Cyclic GMP-AMP synthase (cGAS), a key DNA sensor, detects cytosolic viral DNA and activates the adaptor protein stimulator of interferon genes (STING) to initiate interferon (IFN) production and host innate antiviral responses. Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality in waterfowl. In the present study, we found that DEV inhibits host innate immune responses during the late phase of viral infection. Furthermore, we screened DEV proteins for their ability to inhibit the cGAS-STING DNA-sensing pathway and identified multiple viral proteins, including UL41, US3, UL28, UL53, and UL24, which block IFN-ß activation through this pathway. The DEV tegument protein UL41, which exhibited the strongest inhibitory effect, selectively downregulated the expression of interferon regulatory factor 7 (IRF7) by reducing its mRNA accumulation, thereby inhibiting the DNA-sensing pathway. Ectopic expression of UL41 markedly reduced viral DNA-triggered IFN-ß production and promoted viral replication, whereas deficiency of UL41 in the context of DEV infection increased the IFN-ß response to DEV and suppressed viral replication. In addition, ectopic expression of IRF7 inhibited the replication of the UL41-deficient virus, whereas IRF7 knockdown facilitated its replication. This study is the first report identifying multiple viral proteins encoded by a duck DNA virus, which inhibit the cGAS-STING DNA-sensing pathway. These findings expand our knowledge of DNA sensing in ducks and reveal a mechanism through which DEV antagonizes the host innate immune response. IMPORTANCE Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality, resulting in substantial economic losses in the commercial waterfowl industry. The evasion of DNA-sensing pathway-mediated antiviral innate immunity is essential for the persistent infection and replication of many DNA viruses. However, the mechanisms used by DEV to modulate the DNA-sensing pathway remain poorly understood. In the present study, we found that DEV encodes multiple viral proteins to inhibit the cGAS-STING DNA-sensing pathway. The DEV tegument protein UL41 selectively diminished the accumulation of interferon regulatory factor 7 (IRF7) mRNA, thereby inhibiting the DNA-sensing pathway. Loss of UL41 potently enhanced the IFN-ß response to DEV and impaired viral replication in ducks. These findings provide insights into the host-virus interaction during DEV infection and help develop new live attenuated vaccines against DEV.

Asunto(s)

Alphaherpesvirinae , Patos , Inmunidad Innata , Nucleotidiltransferasas , Proteínas Virales , Animales , ADN Viral/genética , ADN Viral/metabolismo , Enteritis/inmunología , Enteritis/virología , Inmunidad Innata/genética , Factor 7 Regulador del Interferón/genética , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Transducción de Señal , Proteínas Virales/genética , Proteínas Virales/metabolismo , Evasión Inmune/genética , Alphaherpesvirinae/genética , Alphaherpesvirinae/inmunología

RESUMEN

DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling. Whether and how pathogens manipulate cGAS-DNA condensation to mediate immune evasion is unknown. We report the identification of a structurally related viral tegument protein family, represented by ORF52 and VP22 from gamma- and alpha-herpesvirinae, respectively, that employs a conserved mechanism to restrict cGAS-DNA phase separation. ORF52/VP22 proteins accumulate into, and effectively disrupt, the pre-formed cGAS-DNA condensation both in vitro and in cells. The inhibition process is dependent on DNA-induced liquid-liquid phase separation of the viral protein rather than a direct interaction with cGAS. Moreover, highly abundant ORF52 proteins carried within viral particles are able to target cGAS-DNA phase separation in early infection stage. Our results define ORF52/VP22-type tegument proteins as a family of inhibitors targeting cGAS-DNA phase separation and demonstrate a mechanism for how viruses overcome innate immunity.

Asunto(s)

Alphaherpesvirinae , Betaherpesvirinae , ADN , Infecciones por Herpesviridae , Evasión Inmune , Nucleotidiltransferasas , Proteínas Estructurales Virales , Alphaherpesvirinae/química , Alphaherpesvirinae/genética , Alphaherpesvirinae/inmunología , Betaherpesvirinae/química , Betaherpesvirinae/genética , Betaherpesvirinae/inmunología , ADN/química , ADN/genética , ADN/inmunología , Células HEK293 , Células HeLa , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/inmunología , Humanos , Inmunidad Innata , Nucleotidiltransferasas/química , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/inmunología , Proteínas Estructurales Virales/química , Proteínas Estructurales Virales/genética , Proteínas Estructurales Virales/inmunología

RESUMEN

Both the development of the mammalian innate immune system and the antagonistic strategies acquired by alphaherpesviruses to dismantle it have been shaped by co-evolving virus-host interactions over millions of years. Here, we review mechanisms employed by mammalian cells to detect pathogen molecules, such as viral glycoproteins and nucleic acids, and induce innate immune signaling upon infection with alphaherpesviruses. We further explore strategies acquired by these viruses to bypass immune detection and activation, thereby supporting virus replication and spread. Finally, we discuss the contributions of advanced 'omics' and microscopy methods to these discoveries in immune signaling and highlight emerging technologies that can help to further our understanding of the dynamic interplay between host innate immune responses and virus immune evasion.

Asunto(s)

Alphaherpesvirinae/inmunología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Interacciones Huésped-Patógeno/inmunología , Evasión Inmune , Inmunidad Innata , Animales , Evolución Biológica , ADN Viral/genética , ADN Viral/inmunología , Infecciones por Herpesviridae/metabolismo , Humanos , Transducción de Señal , Proteínas Virales/genética , Proteínas Virales/inmunología , Replicación Viral

RESUMEN

Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of enormous preclinical and clinical research. A live viral vaccine for prevention of chickenpox and a subunit therapeutic vaccine to prevent zoster are highly successful. In contrast, progress towards the development of effective prophylactic or therapeutic vaccines against HSV-1 and HSV-2 has met with limited success. This review provides an overview of the successes and failures, the different types of immune responses elicited by various vaccine modalities, and the need to reconsider the preclinical models and immune correlates of protection against HSV.

Asunto(s)

Alphaherpesvirinae/inmunología , Infecciones por Herpesviridae/prevención & control , Vacunas Virales/inmunología , Animales , Infecciones por Herpesviridae/inmunología , Humanos , Inmunidad/inmunología , Vacunas Atenuadas/inmunología , Vacunas de Subunidad/inmunología

RESUMEN

Innate immune system is considered the first line of defense during viral invasion, with the wealth of the literature demonstrating innate immune control of diverse viruses during acute infection. What is far less clear is the role of innate immune system during chronic virus infections. This short review focuses on alphaherpesviruses and gammaherpesviruses, two highly prevalent herpesvirus subfamilies that, following a brief, once in a lifetime period of acute lytic infection, establish life-long latent infection that is characterized by sporadic reactivation in an immunocompetent host. In spite of many similarities, these two viral families are characterized by distinct cellular tropism and pathogenesis. Here we focus on the published in vivo studies to review known interactions of these two viral subfamilies with the innate immunity of the intact host, both during acute and, particularly, chronic virus infection.

Asunto(s)

Alphaherpesvirinae/inmunología , Gammaherpesvirinae/inmunología , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata , Latencia del Virus/inmunología , Alphaherpesvirinae/patogenicidad , Animales , Enfermedad Crónica , Gammaherpesvirinae/patogenicidad , Humanos , Ratones , Replicación Viral/inmunología

RESUMEN

This protocol describes a footpad inoculation model used to study the initiation and development of neuroinflammatory responses during alphaherpesvirus infection in mice. As alphaherpesviruses are main invaders of the peripheral nervous system (PNS), this model is suitable to characterize the kinetics of viral replication, its spread from the PNS to CNS, and associated neuroinflammatory responses. The footpad inoculation model allows virus particles to spread from a primary infection site in the footpad epidermis to sensory and sympathetic nerve fibers that innervate the epidermis, sweat glands, and dermis. The infection spreads via the sciatic nerve to the dorsal root ganglia (DRG) and ultimately through the spinal cord to the brain. Here, a mouse footpad is inoculated with pseudorabies virus (PRV), an alphaherpesvirus closely related to herpes simplex virus (HSV) and varicella-zoster virus (VZV). This model demonstrates that PRV infection induces severe inflammation, characterized by neutrophil infiltration in the footpad and DRG. High concentrations of inflammatory cytokines are subsequently detected in homogenized tissues by ELISA. In addition, a strong correlation is observed between PRV gene and protein expression (via qPCR and IF staining) in DRG and the production of pro-inflammatory cytokines. Therefore, the footpad inoculation model provides a better understanding of the processes underlying alphaherpesvirus-induced neuropathies and may lead to the development of innovative therapeutic strategies. In addition, the model can guide research on peripheral neuropathies, such as multiple sclerosis and associated viral-induced damage to the PNS. Ultimately, it can serve as a cost-effective in vivo tool for drug development.

Asunto(s)

Alphaherpesvirinae/inmunología , Ganglios Espinales/inmunología , Infecciones por Herpesviridae/inmunología , Miembro Posterior/virología , Inflamación/etiología , Enfermedades del Sistema Nervioso Periférico/etiología , Nervio Ciático/inmunología , Animales , Modelos Animales de Enfermedad , Ganglios Espinales/virología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Inflamación/patología , Ratones , Ratones Endogámicos C57BL , Enfermedades del Sistema Nervioso Periférico/patología , Nervio Ciático/virología , Replicación Viral

RESUMEN

Fibropapillomatosis (FP) is a tumor disease associated with a herpesvirus (chelonid herpesvirus 5 [ChHV5]) that affects mainly green turtles globally. Understanding the epidemiology of FP has been hampered by a lack of robust serological assays to monitor exposure to ChHV5. This is due in part to an inability to efficiently culture the virus in vitro for neutralization assays. Here, we expressed two glycoproteins (FUS4 and FUS8) from ChHV5 using baculovirus. These proteins were immobilized on enzyme-linked immunosorbent assay plates in their native form and assayed for reactivity to two types of antibodies, full-length 7S IgY and 5.7S IgY, which has a truncated Fc region. Turtles from Florida were uniformly seropositive to ChHV5 regardless of tumor status. In contrast, in turtles from Hawaii, we detected strong antibody reactivity mainly in tumored animals, with a lower antibody response being seen in nontumored animals, including those from areas where FP is enzootic. Turtles from Hawaii actively shedding ChHV5 were more seropositive than nonshedders. In trying to account for differences in the serological responses to ChHV5 between green turtles from Hawaii and green turtles from Florida, we rejected the cross-reactivity of antibodies to other herpesviruses, differences in viral epitopes, or differences in procedure as likely explanations. Rather, behavioral or other differences between green turtles from Hawaii and green turtles from Florida might have led to the emergence of biologically different viral strains. While the strains from turtles in Florida apparently spread independently of tumors, the transmission of the Hawaiian subtype relies heavily on tumor formation.IMPORTANCE Fibropapillomatosis (FP) is a tumor disease associated with chelonid herpesvirus 5 (ChHV5) that is an important cause of mortality in threatened green turtles globally. FP is expanding in Florida and the Caribbean but declining in Hawaii. We show that Hawaiian turtles mount antibodies to ChHV5 mainly in response to tumors, which are the only sites of viral replication, whereas tumored and nontumored Floridian turtles are uniformly seropositive. Tumor viruses that depend on tumors for replication and spread are rare, with the only example being the retrovirus causing walleye dermal sarcoma in fish. The Hawaiian strain of ChHV5 may be the first DNA virus with such an unusual life history. Our findings, along with the fundamental differences in the life histories between Floridian turtles and Hawaiian turtles, may partly explain the differential dynamics of FP between the two regions.

Asunto(s)

Alphaherpesvirinae/inmunología , Formación de Anticuerpos/inmunología , Tortugas/inmunología , Alphaherpesvirinae/genética , Alphaherpesvirinae/metabolismo , Animales , Virus ADN , Florida , Glicoproteínas/inmunología , Hawaii , Herpesviridae/genética , Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Papiloma/virología , Filogenia , Neoplasias Cutáneas/virología , Infecciones Tumorales por Virus/virología , Tortugas/virología

RESUMEN

Pseudorabies virus (PRV), an alphaherpesvirus closely related to Varicella-Zoster virus (VZV) and Herpes simplex type 1 (HSV1) infects mucosa epithelia and the peripheral nervous system (PNS) of its host. We previously demonstrated that PRV infection induces a specific and lethal inflammatory response, contributing to severe neuropathy in mice. So far, the mechanisms that initiate this neuroinflammation remain unknown. Using a mouse footpad inoculation model, we found that PRV infection rapidly and simultaneously induces high G-CSF and IL-6 levels in several mouse tissues, including the footpad, PNS and central nervous system (CNS) tissues. Interestingly, this global increase occurred before PRV had replicated in dorsal root ganglia (DRGs) neurons and also was independent of systemic inflammation. These high G-CSF and IL-6 levels were not caused by neutrophil infiltration in PRV infected tissues, as we did not detect any neutrophils. Efficient PRV replication and spread in the footpad was sufficient to activate DRGs to produce cytokines. Finally, by using knockout mice, we demonstrated that TLR2 and IFN type I play crucial roles in modulating the early neuroinflammatory response and clinical outcome of PRV infection in mice. Overall, these results give new insights into the initiation of virus-induced neuroinflammation during herpesvirus infections.

Asunto(s)

Alphaherpesvirinae/inmunología , Infecciones por Herpesviridae/inmunología , Inflamación/inmunología , Interferón Tipo I/farmacología , Neuronas/inmunología , Sistema Nervioso Periférico/inmunología , Receptor Toll-Like 2/metabolismo , Alphaherpesvirinae/efectos de los fármacos , Animales , Antivirales/farmacología , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/virología , Inflamación/tratamiento farmacológico , Inflamación/virología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/virología , Sistema Nervioso Periférico/efectos de los fármacos , Sistema Nervioso Periférico/virología , Receptor Toll-Like 2/genética , Replicación Viral

RESUMEN

Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses have a protein-rich layer called the tegument that, connects the DNA-containing capsid to the envelope. Tegument proteins have a variety of functions, playing roles in viral entry, secondary envelopment, viral capsid nuclear transportation during infection, and immune evasion. Recently, many studies have made substantial breakthroughs in characterizing the innate immune evasion of tegument proteins. A wide range of antiviral tegument protein factors that control incoming infectious pathogens are induced by the type I interferon (IFN) signaling pathway and other innate immune responses. In this review, we discuss the immune evasion of tegument proteins with a focus on herpes simplex virus type I.

Asunto(s)

Alphaherpesvirinae/inmunología , Evasión Inmune/inmunología , Inmunidad Innata/inmunología , Proteínas Estructurales Virales/inmunología , Alphaherpesvirinae/metabolismo , Animales , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/metabolismo , Humanos , Transducción de Señal/inmunología , Proteínas Estructurales Virales/metabolismo , Internalización del Virus , Replicación Viral/inmunología

RESUMEN

Pathogens can impact host survival, fecundity, and population dynamics even when no obvious disease is observed. Few baseline data on pathogen prevalence and diversity of caribou are available, which hampers our ability to track changes over time and evaluate impacts on caribou health. Archived blood samples collected from ten migratory caribou herds in Canada and two in Greenland were used to test for exposure to pathogens that have the potential to effect population productivity, are zoonotic or are emerging. Relationships between seroprevalence and individual, population, and other health parameters were also examined. For adult caribou, the highest overall seroprevalence was for alphaherpesvirus (49%, n = 722), pestivirus (49%, n = 572) and Neospora caninum (27%, n = 452). Lower seroprevalence was found for parainfluenza virus type 3 (9%, n = 708), Brucella suis (2%, n = 758), and Toxoplasma gondii (2%, n = 706). No animal tested positive for antibodies against West Nile virus (n = 418) or bovine respiratory syncytial virus (n = 417). This extensive multi-pathogen survey of migratory caribou herds provides evidence that caribou are exposed to pathogens that may have impacts on herd health and revealed potential interactions between pathogens as well as geographical differences in pathogen exposure that could be linked to the bio-geographical history of caribou. Caribou are a keystone species and the socio-economic cornerstone of many indigenous cultures across the North. The results from this study highlight the urgent need for a better understanding of pathogen diversity and the impact of pathogens on caribou health.

Asunto(s)

Anticuerpos Antibacterianos/sangre , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antivirales/sangre , Reno/inmunología , Alphaherpesvirinae/inmunología , Alphaherpesvirinae/patogenicidad , Animales , Brucella/inmunología , Brucella/patogenicidad , Neospora/inmunología , Neospora/patogenicidad , Pestivirus/inmunología , Pestivirus/patogenicidad , Reno/crecimiento & desarrollo , Estudios Seroepidemiológicos

RESUMEN

In this study, we isolated and identified an infectious laryngotracheitis virus (ILTV) that was naturally avirulent in specific pathogen-free (SPF) chickens, with the aim of developing a more efficacious vaccine against ILTV and Newcastle disease virus (NDV). We constructed a US9-deleted ILTV mutant based on this avirulent ILTV, and then constructed a recombinant ILTV (designated ILTV-ΔUS9-F) expressing the fusion protein (F) of the genotype VII NDV based on the US9-deleted ILTV mutant. Expression of the F protein in ILTV-ΔUS9-F-infected cells was confirmed by indirect immunofluorescence assay and western blotting. The inserted F gene was stably expressed in ILTV-ΔUS9-F. The growth kinetics of ILTV-ΔUS9-F were comparable to those of the wild-type ILTV strain. Vaccination of SPF chickens with ILTV-ΔUS9-F produced no clinical signs but did induce low levels of NDV-specific enzyme-linked immunosorbent assay and neutralizing antibodies. A single vaccination with 104 plaque-forming units (PFU) of ILTV-ΔUS9-F provided good protection against both genotype VII and IX NDVs based on clinical signs, similar to the protection provided by the commercial live La Sota vaccine. Notably, ILTV-ΔUS9-F limited the replication and shedding of genotype VII NDV from oropharyngeal swabs more efficiently than the La Sota vaccine. In addition, vaccination with lower doses (103 and 102 PFU) of ILTV-ΔUS9-F also provided sufficient clinical protection. These results indicated that ILTV-ΔUS9-F may be a bivalent vaccine candidate against both ILTV and NDV.

Asunto(s)

Infecciones por Herpesviridae/veterinaria , Enfermedad de Newcastle/prevención & control , Enfermedades de las Aves de Corral/prevención & control , Proteínas Virales de Fusión/inmunología , Alphaherpesvirinae/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Pollos , Genotipo , Infecciones por Herpesviridae/prevención & control , Enfermedad de Newcastle/inmunología , Virus de la Enfermedad de Newcastle/inmunología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/virología , Organismos Libres de Patógenos Específicos , Proteínas Virales de Fusión/genética

RESUMEN

There are several infectious agents of domestic cattle that can also be present in free-living ruminant populations. These include bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus (BVDV) which are the causative agents of infectious bovine rhinotracheitis and bovine viral diarrhea, respectively. The study was conducted on serum samples from 59 red deer, 24 roe deer, and 3 fallow deer (86 in total), originating from two geographically separate areas of Poland. The samples were tested with commercially available ELISA tests for BoHV-1 and BVDV. The overall seroprevalence was 5.8% and 3.5%, respectively. All positive samples originated exclusively from red deer. Because of BoHV-1 ELISA cross reactivity with cervid herpesvirus 1 and 2 (CvHV-1 and -2) the nature of alphaherpesviruses infecting the sampled animals could not be assessed.

Asunto(s)

Alphaherpesvirinae/inmunología , Anticuerpos Antivirales/sangre , Ciervos/sangre , Virus de la Diarrea Viral Bovina/inmunología , Alphaherpesvirinae/clasificación , Animales , Animales Salvajes , Polonia , Seroconversión

RESUMEN

In the present study on Bubalus bubalis of the Campania Region (Italy) the serum levels of derivatives of reactive oxygen metabolites (d-ROMs), anti-ROM and oxidative stress index (Osi) were evaluated. These data were then related to the seropositive status of the animals against alpha-herpesviruses, precisely Bubaline herpesvirus 1 (BuHV-1) and Bovine herpesvirus 1 (BoHV-1). Clinically healthy Mediterranean buffaloes were selected for this study. The serum samples of these animals were taken, and d-ROMs, anti-ROM and Osi were measured using commercially available tests. The preliminary data demonstrated that animals seropositive to both BuHV-1 and BoHV-1 present more oxidative stress than seronegative animals, as revealed by a significant increase in d-ROMs. Our results provide, for the first time, insight into the reac- tive oxygen species (ROS) modulation induced by the herpesvirus in Bubalus bubalis.

Asunto(s)

Alphaherpesvirinae/inmunología , Búfalos/sangre , Infecciones por Herpesviridae/veterinaria , Animales , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/metabolismo , Especies Reactivas de Oxígeno , Estudios Seroepidemiológicos

RESUMEN

Infectious bovine rhinotracheitis (IBR)/infectious pustular vulvovaginitis (IPV) caused by Bovine alphaherpesvirus 1 (BoHV-1) is a significant disease in domestic and wild cattle. In June 2015, the Ministry of Agriculture, Food and Forestry in Italy approved a national surveillance plan to control and eradicate IBR in beef cattle breeds. The objective of this study was to evaluate the results of the first year of the IBR voluntary surveillance plan in Italy. The aim of the plan is to eradicate IBR in all bovines recorded in the National Herd Book for Italian beef cattle breeds over six years. Monetary incentives are used to encourage breeders to achieve the annual seroprevalence ranges stated in the plan. A Ministerial decree states that all bovines in breeding herds and aged older than 12 months should be serologically tested. Serum samples were tested for presence of the antibody to glycoprotein E of BoHV-1 using commercially available enzyme-linked immunosorbent assays. The national herd seroprevalence was 55.49% (95% confidence interval [CI] 52.01-58.92). Of 25,121 bovines tested for antibodies against BoHV-1, 8014 were positive. The seroprevalence in animals from autochthonous Italian cattle breeds was 31.89% (95% CI 31.31-32.47). Seroprevalence was highest in Podolica cattle (55.14%; 95% CI 54.07-56.21), lowest in Maremmana cattle (9.95%; 95% CI 7.99-12.31), and intermediate in Chianina (22.01%; 95% CI 21.03-23.01), Marchigiana (24.85%; 95% CI 23.52-26.23), and Romagnola (15.60%; 95% CI 14.62-16.64) cattle. These seroprevalence rates indicate a need for intervention to decrease the inevitable severe economic losses arising from BoHV-1 infection. Although some regions in Italy have a long history of combatting BoHV-1 infection, only the province of Bolzano has eradicated IBR.

Asunto(s)

Anticuerpos Antivirales/sangre , Erradicación de la Enfermedad/estadística & datos numéricos , Monitoreo Epidemiológico/veterinaria , Rinotraqueítis Infecciosa Bovina/epidemiología , Rinotraqueítis Infecciosa Bovina/inmunología , Alphaherpesvirinae/inmunología , Alphaherpesvirinae/aislamiento & purificación , Animales , Animales Domésticos , Cruzamiento , Bovinos , Erradicación de la Enfermedad/métodos , Ensayo de Inmunoadsorción Enzimática , Femenino , Rinotraqueítis Infecciosa Bovina/virología , Italia/epidemiología , Estudios Seroepidemiológicos

RESUMEN

Duck plague virus (DPV), a member of alphaherpesvirus sub-family, can cause significant economic losses on duck farms in China. DPV Chinese virulent strain (CHv) is highly pathogenic and could induce massive ducks death. Attenuated DPV vaccines (CHa) have been put into service against duck plague with billions of doses in China each year. Researches on DPV have been development for many years, however, a comprehensive understanding of molecular mechanisms underlying pathogenicity of CHv strain and protection of CHa strain to ducks is still blank. In present study, we performed RNA-seq technology to analyze transcriptome profiling of duck spleens for the first time to identify differentially expressed genes (DEGs) associated with the infection of CHv and CHa at 24 h. Comparison of gene expression with mock ducks revealed 748 DEGs and 484 DEGs after CHv and CHa infection, respectively. Gene pathway analysis of DEGs highlighted valuable biological processes involved in host immune response, cell apoptosis and viral invasion. Genes expressed in those pathways were different in CHv infected duck spleens and CHa vaccinated duck spleens. The results may provide valuable information for us to explore the reasons of pathogenicity caused by CHv strain and protection activated by CHa strain.

Asunto(s)

Alphaherpesvirinae/inmunología , Patos/virología , Infecciones por Herpesviridae/veterinaria , Vacunas contra Herpesvirus/uso terapéutico , Enfermedades de las Aves de Corral/prevención & control , Bazo/metabolismo , Animales , Patos/metabolismo , Expresión Génica/inmunología , Perfilación de la Expresión Génica/veterinaria , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/virología , Vacunas contra Herpesvirus/inmunología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/virología , ARN/genética , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/uso terapéutico

RESUMEN

The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity. HSV-1-reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, as well as kill VZV-infected dermal fibroblasts. Mono- and cross-reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV-VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10 to 50%. Based on these findings, we hypothesize that host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens and that cross-reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy.

Asunto(s)

Alphaherpesvirinae/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Reacciones Cruzadas/inmunología , Infecciones por Herpesviridae/inmunología , Presentación de Antígeno/inmunología , Antígenos Virales/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Citocinas/metabolismo , Epítopos de Linfocito T/inmunología , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/virología , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 2/inmunología , Humanos , Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Proteínas Virales/inmunología

RESUMEN

Alphaherpesviruses include human and animal pathogens, such as herpes simplex virus type 1, which establish life-long latent infections with episodes of recurrence. The immunocompetence of the infected host is an important determinant for the outcome of infections with alphaherpesviruses. Recognition of pathogen-associated molecular patterns by pattern recognition receptors is an essential, early step in the innate immune response to pathogens. In recent years, it has been discovered that herpesvirus DNA is a strong inducer of the innate immune system. The viral genome can be recognized in endosomes by TLR9, as well as intracellularly by a variety of DNA sensors, the best documented being cGAS, RNA Pol III, IFI16, and AIM2. These DNA sensors use converging signaling pathways to activate transcription factors, such as IRF3 and NF-κB, which induce the expression of type I interferons and other inflammatory cytokines and activate the inflammasome. This review summarizes the recent literature on the innate sensing of alphaherpesvirus DNA, the mechanisms of activation of the different sensors, their mechanisms of signal transduction, their physiological role in defense against herpesvirus infection, and how alphaherpesviruses seek to evade these responses to allow establishment and maintenance of infection.

Asunto(s)

Alphaherpesvirinae/inmunología , ADN Viral/inmunología , Infecciones por Herpesviridae/inmunología , Inmunidad Innata , Alphaherpesvirinae/genética , Animales , ADN Viral/genética , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/virología , Humanos

Asunto(s)

Alphaherpesvirinae/inmunología , Infecciones por Herpesviridae/inmunología , Latencia del Virus/inmunología , Alphaherpesvirinae/genética , Alphaherpesvirinae/metabolismo , Alphaherpesvirinae/patogenicidad , Animales , Colorado , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/virología , Humanos , Latencia del Virus/genética

RESUMEN

Human alphaherpesviruses (αHHV) - herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) - infect mucosal epithelial cells, establish a lifelong latent infection of sensory neurons, and reactivate intermittingly to cause recrudescent disease. Although chronic αHHV infections co-exist with brisk T-cell responses, T-cell immune suppression is associated with worsened recurrent infection. Induction of αHHV-specific T-cell immunity is complex and results in poly-specific CD4 and CD8 T-cell responses in peripheral blood. Specific T-cells are localized to ganglia during the chronic phase of HSV infection and to several infected areas during recurrences, and persist long after viral clearance. These recent advances hold promise in the design of new vaccine candidates.

Asunto(s)

Alphaherpesvirinae/inmunología , Infecciones por Herpesviridae/inmunología , Inmunidad Celular , Linfocitos T/inmunología , Alphaherpesvirinae/fisiología , Animales , Infecciones por Herpesviridae/virología , Humanos