Species-Specific Differences in Organization of Orthopoxvirus Kelch-Like Proteins

Organization of orthopoxvirus proteins of the kelch superfamily and their genes were analyzed and compared. Complete genomic sequences of variola (VAR), monkeypox (MPV), vaccinia (VAC), and species-specific regions of cowpox (CPV) viruses were used in the work. Despite the multiplicity of kelch-like proteins in orthopoxviruses, their function is still vague. It has been discovered that the genes of orthopoxvirus kelch-like proteins are localized only to the terminal variable regions of the genome and display species-specific differences in the lengths of the proteins they potentially encode. All the genes belonging to kelch superfamily in the genome of VAR, which has the only host–the man, are mutationally destroyed. However, CPV, displaying the widest host range among orthopoxviruses, encode the most numerous set of kelch-like proteins. Weak homologies between kelch-like proteins of one virus were demonstrated as well as high homologies between isologues of different orthopoxvirus species. The comparison performed suggest that CPV virus is most ancient and may be considered as the ancestor of other orthopoxviruses pathogenic for humans.     

Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.     

Clinical presentation,viral kinetics,and management of human monkeypox cases from New Delhi,India 2022

We describe the clinical and demographic characteristics, virological follow-up, and management of five confirmed monkeypox cases from New Delhi, India without any international travel history. The viral load kinetics and viral clearance were estimated in oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), EDTA blood, serum, urine, and various lesion specimens on every fourth day of follow-up ranging from 5 to 24 post onset day (POD) of illness. All five cases presented with mild to moderate-grade intermittent fever, myalgia, and lesions on the genitals, groins, lower limb, trunk, and upper limb. Four cases had non-tender firm lymphadenopathy. No secondary complications or sexually transmitted infections were recorded in these cases except for the presence of viral hepatitis B infection marker hepatitis B virus surface antigen (HBsAg) in one case. All the cases were mild and had a good recovery. A higher viral load was detected in lesion fluid (POD 9), followed by lesion roof (POD 9), urine (POD 5), lesion base (POD 5), and OPS/NPS (POD 5). The monkeypox virus (MPXV) DNA was detected in clinical samples from 5th to 24th POD. These monkeypox cases without international travel history suggest the underdiagnosed monkeypox infection in the community. This emphasizes the need for active surveillance of MPXV in the high-risk population such as men having sex with men and female sex workers.     

The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox Drug Efficacy

As a result of the conducted experimental studies on intranasal challenge of ICR mice, rabbits and miniature pigs (even in the maximum variant) with the doses of 4.0–5.5 lg PFU of monkeypox virus (MPXV), some clinical signs such as purulent conjunctivitis, blepharitis and ruffled fur were found only in mice. The 50% infective dose (_CID₅₀) of MPXV for these animals estimated by the presence of external clinical signs was 4.8 lg PFU, and _LID₅₀ estimated by the virus presence in the lungs of mice 7 days post‐infection taking into account its 10% application in the animal respiratory tract was 1.4 lg PFU. When studying the dynamics of MPXV propagation in mice challenged intranasally with 25 _LID₅₀ of MPXV, the maximum pathogen accumulation was revealed in nasal cavity, lungs and brain: 5.7 ± 0.1, 5.5 ± 0.1 and 5.3 ± 0.3 lg PFU/ml, respectively. The pathomorphological examination of these animals revealed the presence and replication of the pathogen in the traditional primary target cells for MPXV (mononuclear phagocyte system cells and respiratory tract epitheliocytes) as well as in some other types of cells (endothelial cells, reticular cells, connective tissue cells). Our use of these animals to assess the antiviral efficacy of some drugs demonstrated the agreement of the results (a significant positive effect of NIOCH‐14 and ST‐246) with those described in scientific literature, which opens up the prospects of using ICR mice as animal models for monkeypox to develop preventive antismallpox drugs.     

知往鉴今:人感染猴痘史及其非同寻常的2022年多国暴发疫情北大核心CSCD

2022年全球多个非地方性流行国家发生了人感染猴痘(human monkeypox,HMPX)暴发疫情,世界卫生组织(World Health Organization,WHO)评述此次暴发是“非同寻常的(atypical)”。要理解这一评语,就必须对猴痘及HMPX的历史有充分的认识,首先知道什么是“寻常的”暴发。因此,该文系统回顾了猴痘,尤其是HMPX的流行病学史,并结合近期WHO等组织机构,以及专家学者的观点,讨论分析此次疫情非同寻常的表现及可能原因。在为读者呈现64年来发人深省的猴痘病毒与人类互动历史的同时,也提供了HMPX暴发疫情多方面的信息和观点,有助于理解WHO等对当前疫情危险性的评估,认识暴发疫情对未来临床和公共卫生的深远影响。     

Endemic human monkeypox, Democratic Republic of Congo, 2001-2004

By analyzing vesicle fluids and crusted scabs from 136 persons with suspected monkeypox, we identified 51 cases of monkeypox by PCR, sequenced the hemagglutinin gene, and confirmed 94% of cases by virus culture. PCR demonstrated chickenpox in 61 patients. Coinfection with both viruses was found in 1 additional patient.     

Using the Ground Squirrel (Marmota bobak) as an Animal Model to Assess Monkeypox Drug Efficacy

In experiments to study the sensitivity of ground squirrels (Marmota bobak) to monkeypox virus (MPXV) at intranasal challenge, expressed pox‐like clinical symptoms (hyperthermia, lymphadenitis, skin rash all over the body and mucous membranes and others) were observed 7–9 days post‐infection. The 50% infective dose (ID₅₀) of MPXV for these marmots determined by the presence of clinical signs of the disease was 2.2 log₁₀ PFU. Some diseased marmots (about 40%) died 13–22 days post‐infection, and the mortality rate was weakly dependent on MPXV infective dose. Lungs with trachea were primary target organs of marmots challenged intranasally (with ~30 ID₅₀). The pathogen got to secondary target organs of the animals mainly via the lymphatic way (with replication in bifurcation lymph nodes). Lungs with trachea, nasal mucosa and skin were the organs where the maximum MPXV amounts accumulated in these animals. Evidences of the pathogen presence and replication were revealed in these and subcutaneously infected marmots in the traditional primary target cells for MPXV (macrophages and respiratory tract epitheliocytes), as well as in some other cells (endotheliocytes, plasmocytes, fibroblasts, reticular and smooth muscle cells). Our use of this animal species to assess the antiviral efficacy of some drugs demonstrated the agreement of the obtained results with those described in scientific literature, which opens up the prospects of using marmots as animal models for monkeypox to develop therapeutic and preventive anti‐smallpox drugs.     

Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo

A 600-fold increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9.6%) tested negative for monkeypox virus (MPXV) infection. The household attack rate (i.e., rate of persons living with an infected person that develop symptoms of MPXV infection) was 50%. Nine families showed >1 transmission event, and >6 transmission events occurred within this health zone. Mean incubation period was 8 days (range 4–14 days). The high attack rate and transmission observed in this study reinforce the importance of surveillance and rapid identification of monkeypox cases. Community education and training are needed to prevent transmission of MPXV infection during outbreaks.     

Phylogenetic and Ecologic Perspectives of a Monkeypox Outbreak,Southern Sudan, 2005

Identification of human monkeypox cases during 2005 in southern Sudan (now South Sudan) raised several questions about the natural history of monkeypox virus (MPXV) in Africa. The outbreak area, characterized by seasonally dry riverine grasslands, is not identified as environmentally suitable for MPXV transmission. We examined possible origins of this outbreak by performing phylogenetic analysis of genome sequences of MPXV isolates from the outbreak in Sudan and from differing localities. We also compared the environmental suitability of study localities for monkeypox transmission. Phylogenetically, the viruses isolated from Sudan outbreak specimens belong to a clade identified in the Congo Basin. This finding, added to the political instability of the area during the time of the outbreak, supports the hypothesis of importation by infected animals or humans entering Sudan from the Congo Basin, and person-to-person transmission of virus, rather than transmission of indigenous virus from infected animals to humans.