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Cell Reports Apr 2024Seo et al. shed light on virus-host interactions as they reveal how poxvirus A51R stabilizes microtubules in infected cells, which impacts vaccinia virus virulence in...
Seo et al. shed light on virus-host interactions as they reveal how poxvirus A51R stabilizes microtubules in infected cells, which impacts vaccinia virus virulence in mice by potentially inhibiting reactive-oxygen-species-dependent antiviral responses in macrophages.
Topics: Vaccinia virus; Virulence; Microtubules; Viral Proteins; Host-Parasite Interactions; Humans; Animals; Mice
PubMed: 38564336
DOI: 10.1016/j.celrep.2024.114050 -
Acta Medica Indonesiana Jan 2024Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in...
Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.
Topics: Male; Humans; Middle Aged; Adult; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Disease Outbreaks; HIV Infections
PubMed: 38561878
DOI: No ID Found -
Frontiers in Immunology 2024In recent years, oncolytic viruses have emerged as promising agents for treating various cancers. An oncolytic virus is a non-pathogenic virus that, due to genetic... (Review)
Review
In recent years, oncolytic viruses have emerged as promising agents for treating various cancers. An oncolytic virus is a non-pathogenic virus that, due to genetic manipulation, tends to replicate in and cause lysis of cancerous cells while leaving healthy cells unaffected. Among these viruses, vaccinia virus is an attractive platform for use as an oncolytic platform due to its 190 Kb genome with a high capacity for encoding therapeutic payloads. Combining oncolytic VV therapy with other conventional cancer treatments has been shown to be synergistic and more effective than monotherapies. Additionally, OVV can be used as a vector to deliver therapeutic payloads, alone or in combination with other treatments, to increase overall efficacy. Here, we present a comprehensive analysis of preclinical and clinical studies that have evaluated the efficacy of oncolytic vaccinia viruses in cancer immunotherapy. We discuss the outcomes of these studies, including tumor regression rates, overall survival benefits, and long-term responses. Moreover, we provide insights into the challenges and limitations associated with oncolytic vaccinia virus- based therapies, including immune evasion mechanisms, potential toxicities, and the development of resistance.
Topics: Humans; Oncolytic Viruses; Vaccinia virus; Oncolytic Virotherapy; Neoplasms; Immunotherapy
PubMed: 38558795
DOI: 10.3389/fimmu.2024.1272351 -
The Journal of General Virology Mar 2024Cardiac glycosides (CGs) are natural steroid glycosides, which act as inhibitors of the cellular sodium-potassium ATPase pump. Although traditionally considered toxic to...
Cardiac glycosides (CGs) are natural steroid glycosides, which act as inhibitors of the cellular sodium-potassium ATPase pump. Although traditionally considered toxic to human cells, CGs are widely used as drugs for the treatment of cardiovascular-related medical conditions. More recently, CGs have been explored as potential anti-viral drugs and inhibit replication of a range of RNA and DNA viruses. Previously, a compound screen identified CGs that inhibited vaccinia virus (VACV) infection. However, no further investigation of the inhibitory potential of these compounds was performed, nor was there investigation of the stage(s) of the poxvirus lifecycle they impacted. Here, we investigated the anti-poxvirus activity of a broad panel of CGs. We found that all CGs tested were potent inhibitors of VACV replication. Our virological experiments showed that CGs did not impact virus infectivity, binding, or entry. Rather, experiments using recombinant viruses expressing reporter proteins controlled by VACV promoters and arabinoside release assays demonstrated that CGs inhibited early and late VACV protein expression at different concentrations. Lack of virus assembly in the presence of CGs was confirmed using electron microscopy. Thus, we expand our understanding of compounds with anti-poxvirus activity and highlight a yet unrecognized mechanism by which poxvirus replication can be inhibited.
Topics: Humans; Vaccinia virus; Cardiac Glycosides; Vaccinia; Poxviridae; Virus Replication
PubMed: 38546099
DOI: 10.1099/jgv.0.001971 -
Viruses Mar 2024Infection at barrier sites, e.g., skin, activates local immune defenses that limit pathogen spread, while preserving tissue integrity. Phenotypically distinct γδ T...
Infection at barrier sites, e.g., skin, activates local immune defenses that limit pathogen spread, while preserving tissue integrity. Phenotypically distinct γδ T cell populations reside in skin, where they shape immunity to cutaneous infection prior to onset of an adaptive immune response by conventional αβ CD4 (T) and CD8 (T) T cells. To examine the mechanisms used by γδ T cells to control cutaneous virus replication and tissue pathology, we examined γδ T cells after infection with vaccinia virus (VACV). Resident γδ T cells expanded and combined with recruited γδ T cells to control pathology after VACV infection. However, γδ T cells did not play a role in control of local virus replication or blockade of systemic virus spread. We identified a unique wound healing signature that has features common to, but also features that antagonize, the sterile cutaneous wound healing response. Tissue repair generally occurs after clearance of a pathogen, but viral wound healing started prior to the peak of virus replication in the skin. γδ T cells contributed to wound healing through induction of multiple cytokines/growth factors required for efficient wound closure. Therefore, γδ T cells modulate the wound healing response following cutaneous virus infection, maintaining skin barrier function to prevent secondary bacterial infection.
Topics: Humans; Animals; Mice; Skin; Administration, Cutaneous; Poxviridae Infections; Vaccinia virus; Wound Healing; Mice, Inbred C57BL
PubMed: 38543790
DOI: 10.3390/v16030425 -
Viruses Feb 2024Monkeypox virus (MPXV), the pathogen responsible for the infectious disease monkeypox, causes lesions on the skin, lymphadenopathy, and fever. It has posed a global...
Monkeypox virus (MPXV), the pathogen responsible for the infectious disease monkeypox, causes lesions on the skin, lymphadenopathy, and fever. It has posed a global public health threat since May 2022. Highly sensitive and specific detection of MPXV is crucial for preventing the spread of the disease. Argonaute (Ago) is an artificial DNA-guided restriction cleavage enzyme programmable with 5'-phosphorylated ssDNA sequences, which can be developed to specifically detect nucleic acids of pathogens. Here, a Ago-based system was established for the detection of MPXV-specific DNA targeting the F3L gene. A short amplicon of 79 bp could be obtained through a fast PCR procedure, which was completed within 45 min. Two 5'-phosphorylation guide DNAs were designed to guide Ago to cleave the amplicon to obtain an 18 bp 5'-phosphorylation sequence specific to MPXV, not to other orthopoxviruses (cowpox, variola, and vaccinia viruses). The 18 bp sequence guided Ago to cleave a designed probe specific to MPXV to emit fluorescence. With optimized conditions for the Ago-MPXV system, it could be completed in 60 min for the detection of the extracted MPXV DNA with the limit of detection (LOD) of 1.1 copies/reaction and did not depend on expensive instruments. Successful application of the Ago-MPXV system in sensitively detecting MPXV in simulated throat swabs, skin swabs, sera, and wastewater demonstrated the system's good performance. The Ago platform, with high sensitivity and specificity established here, has the potential to prevent the spread of MPXV.
Topics: Humans; Mpox (monkeypox); Pyrococcus furiosus; Monkeypox virus; DNA; Argonaute Proteins
PubMed: 38543748
DOI: 10.3390/v16030382 -
Viruses Feb 2024African swine fever virus (ASFV) belongs to the family of , part of the group of nucleocytoplasmic large DNA viruses (NCLDV). Little is known about the internalization...
African swine fever virus (ASFV) belongs to the family of , part of the group of nucleocytoplasmic large DNA viruses (NCLDV). Little is known about the internalization of ASFV in the host cell and the fusion membrane events that take place at early stages of the infection. Poxviruses, also members of the NCLDV and represented by vaccinia virus (VACV), are large, enveloped, double-stranded DNA viruses. Poxviruses were considered unique in having an elaborate entry-fusion complex (EFC) composed of 11 highly conserved proteins integrated into the membrane of mature virions. Recent advances in methodological techniques have again revealed several connections between VACV EFC proteins. In this study, we explored the possibility of an analogous ASFV EFC by identifying ten candidate proteins exhibiting structural similarities with VACV EFC proteins. This could reveal key functions of these ASFV proteins, drawing attention to shared features between the two virus families, suggesting the potential existence of an ASFV entry-fusion complex.
Topics: Animals; Swine; African Swine Fever; Vaccinia virus; African Swine Fever Virus; Poxviridae; Vaccinia; Sequence Homology
PubMed: 38543715
DOI: 10.3390/v16030349 -
Signal Transduction and Targeted Therapy Mar 2024The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic...
The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.
Topics: Animals; Mice; Orthopoxvirus; Combined Antibody Therapeutics; Vaccinia; Antibodies, Viral; Vaccinia virus
PubMed: 38531869
DOI: 10.1038/s41392-024-01766-8 -
Emerging Infectious Diseases Apr 2024We used pathogen genomics to test orangutan specimens from a museum in Bonn, Germany, to identify the origin of the animals and the circumstances of their death. We...
We used pathogen genomics to test orangutan specimens from a museum in Bonn, Germany, to identify the origin of the animals and the circumstances of their death. We found monkeypox virus genomes in the samples and determined that they represent cases from a 1965 outbreak at Rotterdam Zoo in Rotterdam, the Netherlands.
Topics: Animals; Monkeypox virus; Museums; Genomics; Disease Outbreaks; Germany
PubMed: 38526306
DOI: 10.3201/eid3004.231546 -
Emerging Infectious Diseases Apr 2024In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human...
In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.
Topics: Humans; Animals; Swine; Mpox (monkeypox); Monkeypox virus; Suipoxvirus; Democratic Republic of the Congo; Poxviridae
PubMed: 38526165
DOI: 10.3201/eid3004.231413