Exploring monkeypox virus proteins and rapid detection techniques.

Monkeypox (mpox) is an infectious disease caused by the mpox virus and can potentially lead to fatal outcomes. It resembles infections caused by viruses from other families, challenging identification. The pathogenesis, transmission, and clinical manifestations of mpox and other Orthopoxvirus species are similar due to their closely related genetic material. This review provides a comprehensive discussion of the roles of various proteins, including extracellular enveloped virus (EEV), intracellular mature virus (IMV), and profilin-like proteins of mpox. It also highlights recent diagnostic techniques based on these proteins to detect this infection rapidly.

Reverse Zoonotic Transmission of SARS-CoV-2 and Monkeypox Virus: A Comprehensive Review.

Reverse zoonosis reveals the process of transmission of a pathogen through the human-animal interface and the spillback of the zoonotic pathogen. In this article, we methodically demonstrate various aspects of reverse zoonosis, with a comprehensive discussion of SARS-CoV-2 and MPXV reverse zoonosis. First, different components of reverse zoonosis, such as humans, different pathogens, and numerous animals (poultry, livestock, pets, wild animals, and zoo animals), have been demonstrated. Second, it explains the present status of reverse zoonosis with different pathogens during previous occurrences of various outbreaks, epidemics, and pandemics. Here, we present 25 examples from literature. Third, using several examples, we comprehensively illustrate the present status of the reverse zoonosis of SARS-CoV-2 and MPXV. Here, we have provided 17 examples of SARS-CoV-2 reverse zoonosis and two examples of MPXV reverse zoonosis. Fourth, we have described two significant aspects of reverse zoonosis: understanding the fundamental aspects of spillback and awareness. These two aspects are required to prevent reverse zoonosis from the current infection with two significant viruses. Finally, the One Health approach was discussed vividly, where we urge scientists from different areas to work collaboratively to solve the issue of reverse zoonosis.

Monkeypox: Past, Present, and Future.

Monkeypox (Mpox) is a zoonotic disease caused by a virus (monkeypox virus-MPV) belonging to the Poxviridae family. In humans, the disease has an incubation period of 5-21 days and then progresses in two phases, the prodromal phase and the rash phase. The prodromal phase is characterized by non-specific symptoms such as fever, muscle pain, malaise, lymphadenopathy, headache, and chills. Skin lesions appear in the rash phase of the disease. These lesions progress through different stages (macules, papules, vesicles, and pustules). In May 2022, WHO reported an outbreak of human Mpox in several countries which were previously Mpox-free. As per the CDC report of March 01, 2023, a total of 86,231 confirmed cases of Mpox and 105 deaths have been reported from 110 countries and territories across the globe. Notably, more than 90% of these countries were reporting Mpox for the first time. The phylogenetic analysis revealed that this outbreak was associated with the virus from the West African clade. However, most of the cases in this outbreak had no evidence of travel histories to MPV-endemic countries in Central or West Africa. This outbreak was primarily driven by the transmission of the virus via intimate contact in men who have sex with men (MSM). The changing epidemiology of Mpox raised concerns about the increasing spread of the disease in non-endemic countries and the urgent need to control and prevent it. In this chapter, we present all the documented cases of Mpox from 1970 to 2023 and discuss the past, present, and future of MPV.

Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Biological Characteristics and Pathogenesis of Monkeypox Virus: An Overview.

Although the smallpox virus has been eradicated worldwide, the World Health Organization (WHO) has issued a warning about the virus's potential to propagate globally. The WHO labeled monkeypox a world public health emergency in July 2022, requiring urgent prevention and treatment. The monkeypox virus is a part of the Poxviridae family, Orthopoxvirus genus, and is accountable for smallpox, which has killed over a million people in the past. Natural hosts of the virus include squirrels, Gambian rodents, chimpanzees, and other monkeys. The monkeypox virus has transmitted to humans through primary vectors (various animal species) and secondary vectors, including direct touch with lesions, breathing particles from body fluids, and infected bedding. The viral particles are ovoid or brick-shaped, 200-250 nm in diameter, contain a single double-stranded DNA molecule, and reproduce only in the cytoplasm of infected cells. Monkeypox causes fever, cold, muscle pains, headache, fatigue, and backache. The phylogenetic investigation distinguished between two genetic clades of monkeypox: the more pathogenic Congo Basin clade and the West Africa clade. In recent years, the geographical spread of the human monkeypox virus has accelerated despite a paucity of information regarding the disease's emergence, ecology, and epidemiology. Using lesion samples and polymerase chain reaction (PCR), the monkeypox virus was diagnosed. In the USA, the improved Ankara vaccine can now be used to protect people who are at a higher risk of getting monkeypox. Antivirals that we have now work well against smallpox and may stop the spread of monkeypox, but there is no particular therapy for monkeypox.

Molecular Virology of Orthopoxviruses with Special Reference to Monkeypox Virus.

Poxviruses are large (200-450 nm) and enveloped viruses carrying double-stranded DNA genome with an epidermal cell-specific adaptation. The genus Orthopoxvirus within Poxviridae family constitutes several medically and veterinary important viruses including variola (smallpox), vaccinia, monkeypox virus (MPXV), and cowpox. The monkeypox disease (mpox) has recently emerged as a public health emergency caused by MPXV. An increasing number of human cases of MPXV have been documented in non-endemic nations without any known history of contact with animals brought in from endemic and enzootic regions, nor have they involved travel to an area where the virus was typically prevalent. Here, we review the MPXV replication, virus pathobiology, mechanism of viral infection transmission, virus evasion the host innate immunity and antiviral therapies against Mpox. Moreover, preventive measures including vaccination were discussed and concluded that cross-protection against MPXV may be possible using antibodies that are directed against an Orthopoxvirus. Despite the lack of a specialised antiviral medication, several compounds such as Cidofovir and Ribavirin warrant consideration against mpox.

Human Monkeypox Virus and Host Immunity: New Challenges in Diagnostics and Treatment Strategies.

The monkeypox virus (MPXV), responsible for human disease, has historically been limited to the African countries, with only a few isolated instances reported elsewhere in the world. Nevertheless, in recent years, there have been occurrences of monkeypox in regions where the disease is typically absent, which has garnered global interest. Within a period of less than four months, the incidence of MPXV infections has surged to over 48,000 cases, resulting in a total of 13 deaths. This chapter has addressed the genetics of the pox virus, specifically the human monkeypox virus, and its interaction with the immune systems of host organisms. The present chapter is skillfully constructed, encompassing diagnostic methodologies that span from traditional to developing molecular techniques. Furthermore, the chapter provides a succinct analysis of the therapeutic methods employed, potential future developments, and the various emerging difficulties encountered in illness management.

Treatment and Vaccination for Smallpox and Monkeypox.

The smallpox infection with the variola virus was one of the most fatal disorders until a global eradication was initiated in the twentieth century. The last cases were reported in Somalia 1977 and as a laboratory infection in the UK 1978; in 1980, the World Health Organization (WHO) declared smallpox for extinct. The smallpox virus with its very high transmissibility and mortality is still a major biothreat, because the vaccination against smallpox was stopped globally in the 1980s. For this reason, new antivirals (cidofovir, brincidofovir, and tecovirimat) and new vaccines (ACAM2000, LC16m8 and Modified Vaccine Ankara MVA) were developed. For passive immunization, vaccinia immune globulin intravenous (VIGIV) is available. Due to the relationships between orthopox viruses such as vaccinia, variola, mpox (monkeypox), cowpox, and horsepox, the vaccines (LC16m8 and MVA) and antivirals (brincidofovir and tecovirimat) could also be used in the mpox outbreak with positive preliminary data. As mutations can result in drug resistance against cidofovir or tecovirimat, there is need for further research. Further antivirals (NIOCH-14 and ST-357) and vaccines (VACΔ6 and TNX-801) are being developed in Russia and the USA. In conclusion, further research for treatment and prevention of orthopox infections is needed and is already in progress. After a brief introduction, this chapter presents the smallpox and mpox disease and thereafter full overviews on antiviral treatment and vaccination including the passive immunization with vaccinia immunoglobulins.

Overcoming Stigma: The Human Side of Monkeypox Virus.

Monkeypox (Mpox) virus is a zoonotic disease that was recently declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). Symptoms of Mpox include fever, headache, muscle pain, and a rash which starts on the face and spreads to the rest of the body. The stigma surrounding the Mpox virus has been one of the greatest challenges in dealing with the disease. People with Mpox have been often shunned by their communities, and many are afraid to seek medical care for fear of ostracism. For those affected by the virus, this stigma can significantly impact their mental health and quality of life. It is further fueled by misinformation and societal norms. Hence, a multifaceted approach that includes education, awareness campaigns, and community engagement is needed to overcome the stigma associated with Mpox. Effective communication strategies are critical to the dispelling of rumors and the reduction of fear. Interventional measures need to be shaped according to the needs of those affected.

Monkeypox Outbreak 2022, from a Rare Disease to Global Health Emergence: Implications for Travellers.

Monkeypox (mpox), a zoonotic disease caused by the monkeypox virus (MPXV), poses a significant public health threat with the potential for global dissemination beyond its endemic regions in Central and West Africa. This study explores the multifaceted aspects of monkeypox, covering its epidemiology, genomics, travel-related spread, mass gathering implications, and economic consequences. Epidemiologically, mpox exhibits distinct patterns, with variations in age and gender susceptibility. Severe cases can arise in immunocompromised individuals, underscoring the importance of understanding the factors contributing to its transmission. Genomic analysis of MPXV highlights its evolutionary relationship with the variola virus and vaccinia virus. Different MPXV clades exhibit varying levels of virulence and transmission potential, with Clade I associated with higher mortality rates. Moreover, the role of recombination in MPXV evolution remains a subject of interest, with implications for understanding its genetic diversity. Travel and mass gatherings play a pivotal role in the spread of monkeypox. The ease of international travel and increasing globalization have led to outbreaks beyond African borders. The economic ramifications of mpox outbreaks extend beyond public health. Direct treatment costs, productivity losses, and resource-intensive control efforts can strain healthcare systems and economies. While vaccination and mitigation strategies have proven effective, the cost-effectiveness of routine vaccination in non-endemic countries remains a subject of debate. This study emphasizes the role of travel, mass gatherings, and genomics in its spread and underscores the economic impacts on affected regions. Enhancing surveillance, vaccination strategies, and public health measures are essential in controlling this emerging infectious disease.

Experimental inoculation of pigs with monkeypox virus results in productive infection and transmission to sentinels.

Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.

Understanding the biology of monkeypox virus to prevent future outbreaks.

Historically, monkeypox (mpox) was a zoonotic disease endemic in Africa. However, in 2022, a global outbreak occurred following a substantial increase in cases in Africa, coupled with spread by international travellers to other continents. Between January 2022 and October 2023, about 91,000 confirmed cases from 115 countries were reported, leading the World Health Organization to declare a public health emergency. The basic biology of monkeypox virus (MPXV) can be inferred from other poxviruses, such as vaccinia virus, and confirmed by genome sequencing. Here the biology of MPXV is reviewed, together with a discussion of adaptive changes during MPXV evolution and implications for transmission. Studying MPXV biology is important to inform specific host interactions, to aid in ongoing outbreaks and to predict those in the future.

Monkeypox Virus (MPXV) Infection: A Review.

Monkeypox is a viral disease; its outbreak was recently declared a global emergency by the World Health Organization. For the first time, a monkeypox virus (MPXV)-infected patient was found in India. Various researchers back-to-back tried to find the solution to this health emergency just after COVID-19. In this review, we discuss the current outbreak status of India, its transmission, virulence factors, symptoms, treatment, and the preventive guidelines generated by the Indian Health Ministry. We found that monkeypox virus (MPXV) disease is different from smallpox, and the age group between 30-40 years old is more prone to MPXV disease. We also found that, besides homosexuals, gays, bisexuals, and non-vegetarians, it also affects normal straight men and women who have no history of travel. Close contact should be avoided from rats, monkeys and sick people who are affected by monkeypox. To date, there are no monkeypox drugs, but Tecovirimat is more effective than other drugs that are used for other viral diseases like smallpox. Therefore, we need to develop an effective antiviral agent against the virulence factor of MXPV.

Deadliest mpox outbreak ever sparks a new worry.

Congo cases suggest viral strain there is spreading sexually, like less lethal one that triggered last year's global outbreak.

Isolation and characterization of emerging Mpox virus from India.

Mpox (previously known as Monkeypox) has recently re-emerged, primarily through human-to-human transmission in non-endemic countries including India. Virus isolation is still considered as the gold standard for diagnosis of viral infections. Here, the qPCR positive skin lesion sample from a patient was inoculated in Vero E6 cell monolayer. Characteristic cytopathic effect exhibiting typical cell rounding and detachment was observed at passage-02. The virus isolation was confirmed by qPCR. The replication kinetics of the isolate was determined that revealed maximum viral titre of log 6.3 PFU/mL at 72 h postinfection. Further, whole genome analysis through next generation sequencing revealed that the Mpox virus (MPXV) isolate is characterized by several unique SNPs and INDELs. Phylogenetically, it belonged to A.2 lineage of clade IIb, forming a close group with all other Indian MPXV along with few from USA, UK, Portugal, Thailand and Nigeria. This study reports the first successful isolation and phenotypic and genotypic characterization of MPXV from India.

Viruela símica: una revisión narrativa de la fisiopatología / Monkeypox: a narrative review of pathophysiology

La viruela símica es una enfermedad zoonótica identificada por primera vez en 1958. El virus es un miembro del género Orthopoxvirus, de la familia Poxviridae. Infecta a una amplia variedad de mamíferos, pero se desconoce su reservorio natural. El virus del brote de 2022 pertenece a los clados IIa y IIb. Es probable que la aparición del brote actual se deba a las importaciones del brote de Nigeria de 2017-2018. La propagación de persona a persona puede ocurrir a través del contacto cercano con lesiones, fluidos corporales, gotitas respiratorias y objetos contaminados. Una vez dentro del organismo, el virus infecta las mucosas, células epiteliales y células inmunitarias de los tejidos adyacentes. Luego, el virus se replica y disemina rápidamente a través del sistema hemático y linfático. Las células T desempeñan un papel importante en la regulación de la respuesta inmunitaria contra el virus. Sin embargo, los Orthopoxvirus han desarrollado varios mecanismos para la evasión de la respuesta inmunitaria. La vigilancia de la enfermedad es un factor crucial en la evaluación de riesgo del virus y del control del brote. Para esta revisión se realizó la búsqueda de los principales artículos relacionados a la patogenia del virus, publicados hasta la fecha. El artículo destaca la necesidad de nuevos estudios sobre transmisibilidad y patogenicidad de las cepas asociadas al brote de 2022.

Monkeypox is a zoonotic disease first identified in 1958. The virus is a member of the genus Orthopoxvirus, family Poxviridae. It infects a wide variety of mammals, but its natural reservoir is unknown. The virus in the 2022 outbreak belongs to clades IIa and IIb. The emergence of the current outbreak is likely to be due to importations from the 2017-2018 Nigerian outbreak. Person to person spread can occur through close contact with lesions, body fluids, respiratory droplets and contaminated objects. Once inside the body, the virus infects mucous membranes, epithelial cells and immune cells in adjacent tissues. The virus then replicates and spreads rapidly through the blood and lymphatic system. Tcells play an important role in regulating the immune response against the virus. However, Orthopoxvirus have evolved several mechanisms for evasion of the immune response. Disease surveillance is a crucial factor in virus risk assessment and outbreak control. For this review we searched for the main articles related to the pathogenesis of the virus published to date. The article highlights the need for further studies on transmissibility and pathogenicity of the strains associated with the 2022 outbreak.

Clinical Manifestations of Monkeypox.

Monkeypox is a global health issue caused by the monkeypox virus. It can spread from person to person through respiratory secretions, direct exposure to dermatological lesions of infected patients, or exposure to contaminated objects. It is more common in homosexual men, and most patients are asymptomatic. The gold standard for diagnosis is a real-time polymerase chain reaction. In the absence of testing facilities, clinicians rely upon detailed history to exclude other causes of fever with rashes. Initially, there is a prodrome phase of a few days, which is followed by the appearance of rashes. The dermatological manifestations are in the form of an exanthematous rash, which transforms through a macular, papular, and vesicular phase and disappears after crusting in approximately 3 weeks. There can be associated lymphadenopathy in these patients. Respiratory manifestations include nasal congestion and shortness of breath that may result in secondary bacterial infections. Additionally, patients can have neurological involvement in the form of encephalitis. Furthermore, ocular involvement can occur in the form of conjunctivitis, keratitis, and corneal ulceration. Other symptoms can include diarrhea, vomiting, myalgia, and backache. Since most patients do not require hospitalization, the approach to treatment is mainly vigilant monitoring, antiviral therapy, and management of associated complications.

Making trouble.

The United States is moving to tighten oversight of studies that could make viruses more dangerous. But how far should it go?