The outbreak of monkeypox has become a global matter of concern since last year. Monkeypox is a zoonotic disease caused by monkeypox virus（MPXV）infection，and in addition to the typical symptom of rash，MPXV infection can cause a series of neurological manifestations，with the potential mechanisms of immune-mediated neurological damage after infection and direct invasion of the virus into the nervous system. This article reviews the neurological manifestations of MPXV infection，so as to facilitate the early identification and diagnosis of the neurological complications of MPXV infection and adopt appropriate prevention and treatment measures in a timely manner.
Monkeypox virus

Objective To express the monkeypox virus (MPXV) A23R protein in Escherichia coli and purify by Ni-NTA affinity column, and to prepare mouse antiserum against MPXV A23R. Methods The recombinant plasmid pET-28a-MPXV-A23R was constructed and transformed into Escherichia coli BL21 to induce the expression of A23R protein. After optimizing the conditions of expression, A23R protein was highly expressed. Recombinant A23R protein was purified by Ni-NTA affinity column and identified by Western blot analysis. The purified protein was used to immunize mice for preparing the A23R polyclonal antibody, and the antibody titer was detected by ELISA. Results The expression of A23R recombinant protein reached the peak under the induced conditions of 0.6 mmol/L isopropyl-β-D-thiogalactoside (IPTG), 37 DegreesCelsius and 20 hours. The purity of the protein was about 96.07% and was identified by Western blot analysis. The mice were immunized with recombinant protein, and the titer of antibody reached 1:102 400 at the 6th week after immunization. Conclusion MPXV A23R is expressed highly and purified with a high purity and its antiserum from mouse is obtained with a high titre.
Animals ; Mice ; Monkeypox virus ; Antibodies ; Enzyme-Linked Immunosorbent Assay ; Blotting, Western ; Recombinant Proteins ; Escherichia coli/genetics*

In 2022, the outbreak of human monkeypox (HMPX) occurred in many non-endemic countries. World Health Organization (WHO) assesses that this outbreak is "atypical". The history of monkeypox and HMPX must be reviewed to clearly recognize the "typical" outbreaks to fully understand this comment. Therefore, this paper reviews the epidemiological history of monkeypox, especially HMPX, and discusses and analyzes the atypical manifestations and the possible causes of the present outbreak based on the recent views of WHO, other organizations/institutions, and experts. The text describes the thought-provoking history of the interaction between the monkeypox virus and the human being in the past 64 years, and provides various information and views on the outbreak of HMPX, which is helpful to understand risk assessment and the potential impact of this outbreak on clinical and public health in future.
Animals ; Disease Outbreaks ; Humans ; Monkeypox/epidemiology* ; Monkeypox virus

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
COVID-19 ; Disease Outbreaks/prevention & control* ; Humans ; Monkeypox/epidemiology* ; Monkeypox virus ; Pandemics/prevention & control*

Monkeypox is a zoonosis caused by monkeypox virus. Monkeypox virus belongs to the Orthopoxviruses genus in the Poxviridae family, which is regarded as the most important Orthopoxvirus infection in human beings after the extinction of smallpox. Since the first human monkeypox case was reported in the Democratic Republic of the Congo in 1970, monkeypox has become endemic in Central and West African. From May 6 to July 15, 2022, monkeypox has broken out in many countries. Monkeypox cases have been detected in 62 countries and regions. Moreover, human to human transmission has occurred and attracted high global attention. Monkeypox virus has been discovered for more than 60 years, but the understanding and research of its natural host, epidemiological characteristics and treatment are still relatively limited. Therefore, this study analyzes the epidemic situation, the possible causes of the outbreak and the future key research directions, and puts forward countermeasures to provide scientific basis for the prevention and control of monkeypox.
Animals ; Humans ; Monkeypox virus ; Monkeypox/epidemiology* ; Prevalence ; Poxviridae Infections/epidemiology* ; Zoonoses

OBJECTIVES: The aim of this study was to estimate the medical surge capacity required for mass prophylaxis based on a hypothetical outbreak of smallpox.METHODS: We performed a simulation using the Bioterrorism and Epidemic Outbreak Response Model and varied some important parameters, such as the number of core medical personnel and the number of dispensing clinics.RESULTS: Gaps were identified in the medical surge capacity of the Korean government, especially in the number of medical personnel who could respond to the need for mass prophylaxis against smallpox.CONCLUSIONS: The Korean government will need to train 1,000 or more medical personnel for such an event, and will need to prepare many more dispensing centers than are currently available.
Bioterrorism ; Korea ; Smallpox ; Surge Capacity ; Vaccination ; Variola virus

We have examined isolation and identification protocols for three virus simulant candidates to biological warfare agents. MS2 phage, a simulant for yellow fever virus and Hantaan virus, was propagated using as a host an E. coli strain with F pilus. MS2 phage genome was examined by reverse transcription and polymerase chain reaction (RT-PCR). Coat protein of the phage preparation was examined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometric analysis. Cydia pomonella granulosis virus (CpGV) is a virus simulant candidate to smallpox virus. CpGV was isolated from a commercialized CpGV pellet. In this study, we developed new isolation and identification protocols for CpGV. One disadvantage of using CpGV is that it is not easy to determine viability of the virus. Here, we have included T4 phage as an alternative. We established a high titer production protocol and developed an easy genome identification protocol that does not require purified phage DNA. Stability of these virus preparations was also examined under various storage conditions. When the virus preparations were not subjected to freeze drying, MS2 phage was most stable when it was stored in liquid nitrogen but unstable at 4℃. In contrast, T4 phage was most stable when it was stored at 4℃. CpGV was stable at −20℃ but not at 4℃. Stability during or after freeze drying was also investigated. The result showed that 70~80% MS2 survived the freeze drying process. In contrast, only about 15% of T4 phage survived during the freeze drying. CpGV was found to be degraded during freeze drying.
Bacteriophage T4 ; Bacteriophages ; Biological Warfare Agents ; DNA ; Electrophoresis ; Freeze Drying ; Genome ; Granulovirus ; Hantaan virus ; Levivirus ; Nitrogen ; Polymerase Chain Reaction ; Reverse Transcription ; Variola virus ; Yellow fever virus

Herpes zoster (HZ), or shingles, is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia when VZV-specific T-cell immunity is decreased because of aging or immunosuppression. In the present study, we developed HZ DNA vaccine candidates encoding VZV proteins and cytokine adjuvants, such as IL-7 and IL-33. We immunized C57BL/6 mice with DNA plasmids encoding VZV glycoprotein E (gE), immediate early (IE) 63, or IE62 proteins and found that robust VZV protein-specific T-cell responses were elicited by HZ DNA vaccination. Co-administration of DNA plasmids encoding IL-7 or IL-33 in HZ DNA vaccination significantly enhanced the magnitude of VZV protein-specific T-cell responses. Protective immunity elicited by HZ DNA vaccination was proven by challenge experiments with a surrogate virus, vaccinia virus expressing gE (VV-gE). A single dose of HZ DNA vaccine strongly boosted gE-specific T-cell responses in mice with a history of previous infection by VV-gE. Thus, HZ DNA vaccines with IL-7 and IL-33 adjuvants strongly elicit protective immunity.
Aging ; Animals ; DNA* ; Ganglia, Sensory ; Glycoproteins ; Herpes Zoster* ; Herpesvirus 3, Human ; Immunosuppression ; Interleukin-33* ; Interleukin-7* ; Mice ; Plasmids ; T-Lymphocytes ; Vaccination ; Vaccines, DNA* ; Vaccinia virus

DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-Kb complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.
Administration, Oral ; Animals ; Antigen Presentation* ; Capsaicin* ; Dendritic Cells* ; Lymph Nodes ; Mice ; Ovum ; Sensory Receptor Cells ; T-Lymphocytes ; Vaccinia virus

For rapid and accurate screening of recombinant modified vaccinia virus Ankara (rMVA) that satisfied the quality standards of clinical trials, a novel shuttle vector that can delete the marker gene automatically during virus propagation was construted: pZL-EGFP. To construct the pZL-EGFP, the original shuttle vector pSC11 was modified by replacing the LacZ marker gene with enhanced green fluorescent protein (EGFP) and then inserting homologous sequences of TKL into the flank regions of EGFP. Baby hamster kidney (BHK)-21 cells were cotransfected with pZL-EGFP and MVA, and underwent ten passages and one plaque screening to obtain the EGFP-free rMVA carrying the exogenous gene. Resulting rMVA was tested by polymerase chain reaction and western blotting to verify pZL-EGFP function. A novel shuttle vector pZL-EGFP containing an EGFP marker gene which could be deleted automatically was constructed. This gene deletion had no effect on the activities of rMVA, and the exogenous gene could be expressed stably. These results suggest that rMVA can be packaged efficiently by homologous recombination between pZL-EGFP and MVA in BHK-21 cells, and that the carried EGFP gene can be removed automatically by intramolecular homologous recombination during virus passage. Meanwhile, the gene deletion had no influence on the activities of rMVA and the expression of exogenous target gene. This study lays a solid foundation for the future research.
Animals ; Biomarkers ; Cricetinae ; Epithelial Cells ; virology ; Gene Deletion ; Genetic Engineering ; methods ; Genetic Vectors ; genetics ; metabolism ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Recombination, Genetic ; Vaccinia ; virology ; Vaccinia virus ; genetics ; physiology ; Virus Replication