Human Monkeypox Infection: A Family Cluster in the Midwestern United States

Sejvar, James J.; Chowdary, Yalamanchali; Schomogyi, Mark; Stevens, James; Patel, Jayesh; Karem, Kevin L.; Fischer, Marc; Kuehnert, Matthew J.; Zaki, Sherif R.; Paddock, Christopher D.; Guarner, Jeannette; Shieh, Wun‐Ju; Patton, Joanne L.; Bernard, Nikeva; Liu, Yu; Olson, Victoria A.; Kline, Richard L.; Loparev, Vladimir N.; Schmid, Daniela; Beard, Bradley; Regnery, Russell R.; Damon, Inger K.

doi:10.1086/425039

Cited by 229 publications

(248 citation statements)

References 24 publications

Supporting

Mentioning

225

Contrasting

Unclassified

Order By: Relevance

“…VCP is a known virulence factor of vaccinia (54), and the variola homolog SPICE (for smallpox inhibitor of complement enzyme) is a more potent complement inhibitor (82). It has been proposed that the limited severity of the monkeypox outbreak in the United States in 2003 was because the causative virus was of West African origin (49,85), and the West African clade of monkeypox is significantly less virulent than Congo basin strains (62). This milder virulence of the West African clade is possibly due to the deletion of the monkeypox VCP homolog (MOSPICE) (63).…”

Section: Discussionmentioning

confidence: 99%

Vaccinia Virus Extracellular Enveloped Virion Neutralization In Vitro and Protection In Vivo Depend on Complement

Benhnia

McCausland

Moyron

et al. 2009

J Virol

100

171

View full text Add to dashboard Cite

Antibody neutralization is an important component of protective immunity against vaccinia virus (VACV).Two distinct virion forms, mature virion and enveloped virion (MV and EV, respectively), possess separate functions and nonoverlapping immunological properties. In this study we examined the mechanics of EV neutralization, focusing on EV protein B5 (also called B5R). We show that neutralization of EV is predominantly complement dependent. From a panel of high-affinity anti-B5 monoclonal antibodies (MAbs), the only potent neutralizer in vitro (90% at 535 ng/ml) was an immunoglobulin G2a (IgG2a), and neutralization was complement mediated. This MAb was the most protective in vivo against lethal intranasal VACV challenge. Further studies demonstrated that in vivo depletion of complement caused a >50% loss of anti-B5 IgG2a protection, directly establishing the importance of complement for protection against the EV form. However, the mechanism of protection is not sterilizing immunity via elimination of the inoculum as the viral inoculum consisted of a purified MV form. The prevention of illness in vivo indicated rapid control of infection. We further demonstrate that antibody-mediated killing of VACV-infected cells expressing surface B5 is a second protective mechanism provided by complement-fixing anti-B5 IgG. Cell killing was very efficient, and this effector function was highly isotype specific. These results indicate that anti-B5 antibody-directed cell lysis via complement is a powerful mechanism for clearance of infected cells, keeping poxvirus-infected cells from being invisible to humoral immune responses. These findings highlight the importance of multiple mechanisms of antibody-mediated protection against VACV and point to key immunobiological differences between MVs and EVs that impact the outcome of infection.Vaccines are one of the most cost-effective medical treatments in modern civilization (80). A smallpox vaccine was the first human vaccine, and the modern smallpox vaccine, live vaccinia virus (VACV), is the most successful human vaccine, bringing about the worldwide eradication of smallpox disease due to a heroic World Health Organization campaign in the 1960s and 1970s (27). Elucidating the immunobiology underlying the protection provided by the smallpox vaccine will continue to reveal vaccinology principles that can be applied to future vaccine development against other infectious scourges (95). Neutralizing antibodies are of primary importance in the protection from smallpox provided by the smallpox vaccine in animal models (6,25,33,64) and humans (4). Vaccinia immune globulin (VIG) has been shown to be an effective treatment against smallpox (45) as it was able to reduce the number of smallpox cases by ϳ80% among exposed individuals in four case-controlled studies (42,45,50,51,66).Neutralizing antibodies confer protection mainly through the recognition of structures on the surface of virus particles, and therefore antiviral antibodies directed against the surface of virions are of primary inter...

show abstract

Section: Discussionmentioning

confidence: 99%

Vaccinia Virus Extracellular Enveloped Virion Neutralization In Vitro and Protection In Vivo Depend on Complement

Benhnia

McCausland

Moyron

et al. 2009

J Virol

100

171

View full text Add to dashboard Cite

show abstract

“…During the time the program has been in place, the most frequent differential diagnosis has been varicella-zoster infection. This program was instrumental in studying a cluster of monkeypox infections that occurred during the summer of 2003 in the U.S. and proved the beneficial public health effect of having in place systems that can detect bioterrorism agents (CDC 2003;Sejvar et al 2004). …”

Section: Viral Hemorrhagic Feversmentioning

confidence: 99%

Histopathology and Immunohistochemistry in the Diagnosis of Bioterrorism Agents

Guarner

Zaki

2006

J Histochem Cytochem.

Self Cite

View full text Add to dashboard Cite

From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bioterrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bioterrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).

show abstract

“…The first documented episode of human monkeypox outside the African continent occurred in 2003 in the Midwestern United States [92,[136][137][138][139][140]. The infection that occurred in the USA appeared to be milder than the disease described in the DRC.…”

Section: Persistence and Re-emergence Of Orthopoxviruses In Naturementioning

confidence: 99%

When good vaccines go wild: Feral Orthopoxvirus in developing countries and beyond

Moussatché

Damaso

McFadden

2008

J Infect Dev Ctries

View full text Add to dashboard Cite

The presence of zoonotic poxviruses in nature represents a potential human health risk that has to be re-evaluated by health authorities not only in developing countries, but also in many developed countries. For example, buffalopox virus infection remains to be a threat to humans and cattle in India, and monkeypox virus infection persists in several inhabited places in Africa and, more recently, in the USA. There are also a great number of zoonotic transmissions of cowpox virus from cats to humans in Europe. For almost a decade in Brazil, vaccinia-like viruses have been isolated from human and cattle infections. This review examines the ability of potentially pathogenic orthopoxviruses, including feral versions of vaccinia virus vaccine, to persist in nature and re-emerge for reasons we do not yet understand.

show abstract

Human Monkeypox Infection: A Family Cluster in the Midwestern United States

Cited by 229 publications

References 24 publications

Vaccinia Virus Extracellular Enveloped Virion Neutralization In Vitro and Protection In Vivo Depend on Complement

Vaccinia Virus Extracellular Enveloped Virion Neutralization In Vitro and Protection In Vivo Depend on Complement

Histopathology and Immunohistochemistry in the Diagnosis of Bioterrorism Agents

When good vaccines go wild: Feral Orthopoxvirus in developing countries and beyond

Contact Info

Product

Resources

About