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Journal of Medical Virology May 2024Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with... (Observational Study)
Observational Study
Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.
Topics: Humans; Brazil; Male; Female; Disease Outbreaks; Adult; Young Adult; Adolescent; Middle Aged; Animals; Zoonoses; Herpesvirus 3, Human; Child; HIV Infections; Antibodies, Viral; Aged; Immunoglobulin G
PubMed: 38654686
DOI: 10.1002/jmv.29621 -
Journal of Pediatric Hematology/oncology Jul 2024We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two...
We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two patients were treated with intravenous immunoglobulins; one had a slow hematologic recovery, and the other was rescued by allogeneic hematopoietic stem cell transplantation (HSCT). Of the 2 patients treated with immunosuppressive therapy with antithymocyte globulin and cyclosporine, one had a complete response, and the other was transplanted for nonresponse. One patient underwent a primary allograft. All patients are alive. This study demonstrated that VZV-associated BMF is a life-threatening disorder that often requires HSCT.
Topics: Humans; Male; Female; Varicella Zoster Virus Infection; Child; Hematopoietic Stem Cell Transplantation; Child, Preschool; Herpesvirus 3, Human; Bone Marrow Failure Disorders; Vaccination; Bone Marrow Diseases; Chickenpox Vaccine; Adolescent; Immunoglobulins, Intravenous; Infant
PubMed: 38652069
DOI: 10.1097/MPH.0000000000002866 -
Human Vaccines & Immunotherapeutics Dec 2024Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly... (Review)
Review
Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.
Topics: Humans; Vaccines, Attenuated; HIV Infections; Herpes Zoster Vaccine; Vaccines, Synthetic; Herpes Zoster; Vaccines, Inactivated; Immunogenicity, Vaccine; Vaccine Efficacy; Herpesvirus 3, Human; Adult; Child; Vaccination; Chickenpox Vaccine
PubMed: 38650460
DOI: 10.1080/21645515.2024.2341456 -
Frontiers in Immunology 2024Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which...
Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which () and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker -BoHV-1 combined vaccine based on the HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4, CD8, and CD19 cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 10 CFU of HB150 and 1.0 × 10 TCID BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 10 CFU of HB150 and 1.0 × 10 TCID BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an -BoHV-1 combined vaccine for application in the cattle industry.
Topics: Animals; Cattle; Herpesvirus 1, Bovine; Vaccines, Combined; Vaccines, Attenuated; Mycoplasma bovis; Viral Vaccines; Bacterial Vaccines; Cytokines; Antibodies, Viral; Antibodies, Bacterial; Mycoplasma Infections; Vaccines, Marker; Vaccination; Vaccine Efficacy; Immunity, Humoral; Bovine Respiratory Disease Complex
PubMed: 38646533
DOI: 10.3389/fimmu.2024.1367253 -
Virus Research Jul 2024Although all herpesviruses utilize a highly conserved replication machinery to amplify their viral genomes, different members may have unique strategies to modulate the...
Although all herpesviruses utilize a highly conserved replication machinery to amplify their viral genomes, different members may have unique strategies to modulate the assembly of their replication components. Herein, we characterize the subcellular localization of seven essential replication proteins of varicella-zoster virus (VZV) and show that several viral replication enzymes such as the DNA polymerase subunit ORF28, when expressed alone, are localized in the cytoplasm. The nuclear import of ORF28 can be mediated by the viral DNA polymerase processivity factor ORF16. Besides, ORF16 could markedly enhance the protein abundance of ORF28. Noteworthily, an ORF16 mutant that is defective in nuclear transport still retained the ability to enhance ORF28 abundance. The low abundance of ORF28 in transfected cells was due to its rapid degradation mediated by the ubiquitin-proteasome system. We additionally reveal that radicicol, an inhibitor of the chaperone Hsp90, could disrupt the interaction between ORF16 and ORF28, thereby affecting the nuclear entry and protein abundance of ORF28. Collectively, our findings imply that the cytoplasmic retention and rapid degradation of ORF28 may be a key regulatory mechanism for VZV to prevent untimely viral DNA replication, and suggest that Hsp90 is required for the interaction between ORF16 and ORF28.
Topics: Herpesvirus 3, Human; Humans; Viral Proteins; Virus Replication; Active Transport, Cell Nucleus; DNA-Directed DNA Polymerase; Cell Nucleus; Cytoplasm; Cell Line; DNA Replication
PubMed: 38643859
DOI: 10.1016/j.virusres.2024.199379 -
European Journal of Medicinal Chemistry May 2024New acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared...
Synthesis of LAVR-289, a new [(Z)-3-(acetoxymethyl)-4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug with pronounced antiviral activity against DNA viruses.
New acyclic pyrimidine nucleoside phosphonate prodrugs with a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid skeleton (O-DAPy nucleobase) were prepared through a convergent synthesis by olefin cross-metathesis as the key step. Several acyclic nucleoside 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl]phosphonic acid prodrug exhibited in vitro antiviral activity in submicromolar or nanomolar range against varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus (VV), with good selective index (SI). Among them, the analogue 9c (LAVR-289) proved markedly inhibitory against VZV wild-type (TK+) (EC 0.0035 μM, SI 740) and for thymidine kinase VZV deficient strains (EC 0.018 μM, SI 145), with a low morphological toxicity in cell culture at 100 μM and acceptable cytostatic activity resulting in excellent selectivity. Compound 9c exhibited antiviral activity against HCMV (EC 0.021 μM) and VV (EC 0.050 μM), as well as against HSV-1 (TK-) (EC 0.0085 μM). Finally, LAVR-289 (9c) deserves further (pre)clinical investigations as a potent candidate broad-spectrum anti-herpesvirus drug.
Topics: Antiviral Agents; Prodrugs; Humans; DNA Viruses; Microbial Sensitivity Tests; Structure-Activity Relationship; Herpesvirus 1, Human; Molecular Structure; Herpesvirus 3, Human; Organophosphonates; Cytomegalovirus; Dose-Response Relationship, Drug; Vaccinia virus; Herpesvirus 2, Human
PubMed: 38643669
DOI: 10.1016/j.ejmech.2024.116412 -
BMJ Case Reports Apr 2024Herpes zoster is a disease caused by the reactivation of dormant varicella zoster virus present in the sensory root ganglion. It presents with a vesicular rash on an...
Herpes zoster is a disease caused by the reactivation of dormant varicella zoster virus present in the sensory root ganglion. It presents with a vesicular rash on an erythematous base similar to that seen in classical varicella, however, with only a single dermatomal distribution. The rash is usually seen throughout the affected dermatome as the dorsal root ganglia for each dermatome are clustered together. We present a case of an otherwise healthy male who developed a vesicular rash confined to the distribution of the posterior division of the mandibular nerve. Though the entire mandibular nerve arises from a single ganglion, the skin area supplied by the anterior division of the mandibular nerve was spared. This case provides evidence to show that there is anatomic segregation of cell bodies of nerves traversing anterior and posterior divisions of mandibular division in the trigeminal ganglion and that partial involvement of a sensory root ganglion is possible in immunocompetent patients.
Topics: Humans; Male; Herpesvirus 3, Human; Herpes Zoster; Trigeminal Nerve; Chickenpox; Exanthema
PubMed: 38642932
DOI: 10.1136/bcr-2023-259276 -
Journal of Virology May 2024Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range...
Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range including humans. PRV has developed a variety of strategies to antagonize host antiviral innate immunity. However, the underlying mechanisms have not been fully elucidated. In our previous work, we demonstrated that non-muscle myosin heavy chain IIA (NMHC-IIA), a multifunctional cytoskeleton protein, attenuates innate immune responses triggered by RNA viruses. In the current study, we reported a previously unrecognized role of NMHC-IIA in counteracting PRV-induced cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) production. Mechanistically, PRV infection led to an elevation of NMHC-IIA, strengthening the interaction between poly (ADP-ribose) polymerase 1 (PARP1) and cGAS. This interaction impeded cGAS recognition of PRV DNA and hindered downstream signaling activation. Conversely, inhibition of NMHC-IIA by Blebbistatin triggered innate immune responses and enhanced resistance to PRV proliferation both and . Taken together, our findings unveil that PRV utilizes NMHC-IIA to antagonize host antiviral immune responses via impairing DNA sensing by cGAS. This in-depth understanding of PRV immunosuppression not only provides insights for potential PRV treatment strategies but also highlights NMHC-IIA as a versatile immunosuppressive regulator usurped by both DNA and RNA viruses. Consequently, NMHC-IIA holds promise as a target for the development of broad-spectrum antiviral drugs.IMPORTANCECyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis plays a vital role in counteracting alphaherpesvirus infections. Alphaherpesviruses exploit various strategies for antagonizing cGAS-STING-mediated antiviral immune responses. However, limited examples of pseudorabies virus (PRV)-caused immunosuppression have been documented. Our findings reveal a novel role of non-muscle myosin heavy chain IIA (NMHC-IIA) in suppressing PRV-triggered innate immune responses to facilitate viral propagation both and . In detail, NMHC-IIA recruits poly (ADP-ribose) polymerase 1 (PARP1) to augment its interaction with cGAS, which impairs cGAS recognition of PRV DNA. Building on our previous demonstration of NMHC-IIA's immunosuppressive role during RNA virus infections, these findings indicate that NMHC-IIA acts as a broad-spectrum suppressor of host antiviral innate immunity in response to both DNA and RNA viruses. Therefore, NMHC-IIA will be a promising target for the development of comprehensive antiviral strategies.
Topics: Animals; Humans; Mice; Cell Line; DNA, Viral; HEK293 Cells; Herpesvirus 1, Suid; Immunity, Innate; Interferon Type I; Myosin Heavy Chains; Nonmuscle Myosin Type IIA; Nucleotidyltransferases; Poly (ADP-Ribose) Polymerase-1; Pseudorabies; Signal Transduction; Swine
PubMed: 38639486
DOI: 10.1128/jvi.00483-24 -
Virologica Sinica Jun 2024The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts...
The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.
Topics: Herpesvirus 1, Suid; Virus Replication; Animals; Cell Line; Swine; Tryptophan-tRNA Ligase; Pseudorabies; Signal Transduction; Mitochondria; Host-Pathogen Interactions; Mice
PubMed: 38636706
DOI: 10.1016/j.virs.2024.04.003 -
European Journal of Paediatric... May 2024Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. An intrathecal IgM synthesis is associated with a more rapid progression of MS...
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. An intrathecal IgM synthesis is associated with a more rapid progression of MS and the intrathecal immune response to measles -, rubella -and varicella zoster virus (MRZR) which, if present, increases the likelihood of a diagnosis of MS in adults.
OBJECTIVE
To evaluate the frequency of an intrathecal IgM synthesis and MRZR in children with MS. MethodsChildren with MS and a data set including clinical and treatment history, MRI at onset, in addition to a CSF analysis, and determination of antibody index (AI) of measles, rubella, and zoster antibodies, were eligible. The presence of an intrathecal IgM synthesis and/or a positive MRZ reaction were compared to biomarkers of a more progressive disease course.
RESULTS
In 75 children with MS, OCBs were present in 93.3 %). 49,2 % experienced their first relapse within 6 months. 50.7 % had a total lesion load of more than 10 lesions in the first brain MRI. Spinal lesions were identified in 64 %. 23.5 % had a positive MRZR and 40.3 % an intrathecal IgM synthesis. No significant associations were detected between the presence of an intrathecal IgM synthesis and MRZR and parameters including the relapse rate in the first two years.
CONCLUSION
An intrathecal IgM synthesis and a positive MRZR are found in a subset of MS children but are not associated with markers associated with a poor prognosis.
Topics: Humans; Male; Immunoglobulin M; Child; Female; Multiple Sclerosis; Adolescent; Magnetic Resonance Imaging; Herpesvirus 3, Human; Antibodies, Viral; Child, Preschool; Measles virus; Rubella virus; Disease Progression; Brain; Biomarkers
PubMed: 38636242
DOI: 10.1016/j.ejpn.2024.04.005