Whitni Davidson

National Center for Emerging and Zoonotic Infectious Diseases

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Inger K. Damon

Centers for Disease Control and Prevention

Kimberly Wilkins

Centers for Disease Control and Prevention

Andrea M. McCollum

Centers for Disease Control and Prevention

Yu Li

Centers for Disease Control and Prevention

Mary G. Reynolds

National Center for Emerging and Zoonotic Infectious Diseases

Kevin L. Karem

United States Food and Drug Administration

Christina L. Hutson

Centers for Disease Control and Prevention

Scott K. Smith

Centers for Disease Control and Prevention

Hui Zhao

Hunan University

Christine M. Hughes

Centers for Disease Control and Prevention

Cooperative Institutions

Centers for Disease Control and Prevention

312

National Center for Emerging and Zoonotic Infectious Diseases

139

Computer Emergency Response Team

124

Center for Surveillance, Epidemiology, and Laboratory Services

AID Atlanta

Epidemic Intelligence Service

Emory University

CDC Foundation

Nigeria Centre for Disease Control

California Department of Public Health

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Mpox Specimen Collection, Storage, Preparation, and Laboratory Diagnostics by PCR

Methods in molecular biology (2024)

David Lowe Whitni Davidson Kimberly Wilkins Nicolle Baird

10.1007/978-1-0716-4160-6_2

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Citations (0)

Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Crystal M. Gigante Matthew Plumb Ali Ruprecht Hui Zhao Vaughn Wicker

Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3’ terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance.

Monkeypox

genomic DNA

10.1101/2022.09.16.508251

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Citations (21)

Multiple lineages of Monkeypox virus detected in the United States, 2021- 2022

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Crystal M. Gigante Bette Korber Matthew H. Seabolt Kimberly Wilkins Whitni Davidson

Abstract Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution.

Monkeypox

Orthopoxvirus

10.1101/2022.06.10.495526

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Citations (33)

A tale of two clades: monkeypox viruses

Journal of General Virology (2005)

Anna Likos Scott A. Sammons Victoria A. Olson A. Michael Frace Yu Li

Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.

Monkeypox

Orthopoxvirus

10.1099/vir.0.81215-0

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Citations (732)

Evaluation of smallpox vaccines using variola neutralization

Journal of General Virology (2009)

Inger K. Damon Whitni Davidson Christine M. Hughes Victoria A. Olson Scott K. Smith

The search for a ‘third’-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific ‘ in vitro ’ activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

Variola virus

Smallpox vaccine

Modified vaccinia Ankara

Smallpox virus

Poxviridae

10.1099/vir.0.010553-0

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Citations (49)

Severe Monkeypox in Hospitalized Patients — United States, August 10–October 10, 2022

MMWR Morbidity and Mortality Weekly Report (2022)

Maureen J. Miller Shama Cash‐Goldwasser Grace E. Marx Caroline A. Schrodt Anne Kimball

¶ A list of severe manifestations of monkeypox can be found at https://emergency

Monkeypox

10.15585/mmwr.mm7144e1

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Citations (164)

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

Emerging infectious diseases (2013)

Yoshinori Nakazawa Ginny L. Emerson Darin S. Carroll Hui Zhao Yu Li

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.

Monkeypox

Natural reservoir

10.3201/eid1902.121220

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Citations (79)

Novel Orthopoxvirus Infection in an Alaska Resident

Clinical Infectious Diseases (2017)

Yuri P. Springer Christopher H. Hsu Zachary R. Werle Link E. Olson Michael P. Cooper

Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of population-level immunity. In July 2015, a female resident of interior Alaska presented to an urgent care clinic with a dermal lesion consistent with poxvirus infection. Laboratory testing of a virus isolated from the lesion confirmed infection by an Orthopoxvirus.The virus isolate was characterized by using electron microscopy and nucleic acid sequencing. An epidemiologic investigation that included patient interviews, contact tracing, and serum testing, as well as environmental and small-mammal sampling, was conducted to identify the infection source and possible additional cases.Neither signs of active infection nor evidence of recent prior infection were observed in any of the 4 patient contacts identified. The patient's infection source was not definitively identified. Potential routes of exposure included imported fomites from Azerbaijan via the patient's cohabiting partner or wild small mammals in or around the patient's residence. Phylogenetic analyses demonstrated that the virus represents a distinct and previously undescribed genetic lineage of Orthopoxvirus, which is most closely related to the Old World orthopoxviruses.Investigation findings point to infection of the patient after exposure in or near Fairbanks. This conclusion raises questions about the geographic origins (Old World vs North American) of the genus Orthopoxvirus. Clinicians should remain vigilant for signs of poxvirus infection and alert public health officials when cases are suspected.

Orthopoxvirus

Contact tracing

Variola virus

Monkeypox

Poxviridae

10.1093/cid/cix219

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Citations (71)

An Investigation of a Cluster of Parapoxvirus Cases in Missouri, Feb–May 2006: Epidemiologic, Clinical and Molecular Aspects

Animals (2013)

Edith Lederman Min Tao Mary G. Reynolds Yu Li Hui Zhao

In the spring of 2006, four human cases of parapoxvirus infections in Missouri residents were reported to the Centers for Disease Control and Prevention (CDC), two of which were initially diagnosed as cutaneous anthrax. This investigation was conducted to determine the level of recognition of zoonotic parapoxvirus infections and prevention measures, the degree to which veterinarians may be consulted on human infections and what forces were behind this perceived increase in reported infections. Interviews were conducted and clinical and environmental sampling was performed. Swab and scab specimens were analyzed by real-time polymerase chain reaction (PCR), whereas serum specimens were evaluated for parapoxvirus antibodies. Three case patients were found to have fed ill juvenile animals without using gloves. Forty-six percent of veterinarians reported having been consulted regarding suspected human orf infections. Orf virus DNA was detected from five of 25 asymptomatic sheep. Analysis of extracellular envelope gene sequences indicated that sheep and goat isolates clustered in a species-preferential fashion. Parapoxvirus infections are common in Missouri ruminants and their handlers. Infected persons often do not seek medical care; some may seek advice from veterinarians rather than physicians. The initial perception of increased incidence in Missouri may have arisen from a reporting artifact stemming from heightened concern about anthrax. Asymptomatic parapoxvirus infections in livestock may be common and further investigation warranted.

Disease Control

10.3390/ani3010142

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Citations (10)

Analysis of Variola and Vaccinia Virus Neutralization Assays for Smallpox Vaccines

Clinical and Vaccine Immunology (2012)

Christine M. Hughes Frances K. Newman Whitni Davidson Victoria A. Olson Scott K. Smith

ABSTRACT Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

Variola virus

Smallpox vaccine

Modified vaccinia Ankara

Smallpox virus

10.1128/cvi.00056-12

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Citations (18)