Smallpox and Related Poxvirus Infections in the Simian Host

Hahon, Nicholas

doi:10.1128/mmbr.25.4.459-476.1961

Cited by 23 publications

(18 citation statements)

References 17 publications

(27 reference statements)

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“…Alternatively, it is possible that infection occurs first through the lymphatic system rather than airway epithelia. Previous work provided evidence for both routes (16,17,33,41,57). We also wonder if the increased efficiency of basolateral compared to apical infection might facilitate infection of airway epithelia during the secondary viremia that occurs after replication in the lymphoid system and prior to extracellular shedding.…”

Section: Discussionmentioning

confidence: 97%

“…Variola virus infection occurs following the inhalation of virus-laden airborne droplets (7, 12, 13a, 34). Virus replication within the lung and lymphoid system is followed by viremia (16,41,57). Patients remain asymptomatic during the 7-to 17-daylong incubation period, after which symptoms develop, including fever, malaise, and head and body aches, followed by oropharyngeal lesions and skin rash 2 to 4 days later.…”

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confidence: 99%

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Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Vermeer

McHugh

Rokhlina

et al. 2007

J Virol

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Variola virus, the causative agent of smallpox, enters and exits the host via the respiratory route. To better understand the pathogenesis of poxvirus infection and its interaction with respiratory epithelia, we used vaccinia virus and examined its interaction with primary cultures of well-differentiated human airway epithelia. We found that vaccinia virus preferentially infected the epithelia through the basolateral membrane and released viral progeny across the apical membrane. Despite infection and virus production, epithelia retained tight junctions, transepithelial electrical conductance, and a steep transepithelial concentration gradient of virus, indicating integrity of the epithelial barrier. In fact, during the first four days of infection, epithelial height and cell number increased. These morphological changes and maintenance of epithelial integrity required vaccinia virus growth factor, which was released basolaterally, where it activated epidermal growth factor 1 receptors. These data suggest a complex interaction between the virus and differentiated airway epithelia; the virus preferentially enters the cells basolaterally, exits apically, and maintains epithelial integrity by stimulating growth factor receptors.The threat of bioterrorism has raised concern that smallpox could reemerge as a significant disease entity (10,21,46). The large population of unvaccinated individuals, the many immunocompromised people, and the lack of good treatments suggest that variola virus, the causative agent of smallpox, has the potential for extensive and rapid spread. Thus, there is a renewed interest in understanding poxvirus pathogenesis.Variola virus infection occurs following the inhalation of virus-laden airborne droplets (7, 12, 13a, 34). Virus replication within the lung and lymphoid system is followed by viremia (16,41,57). Patients remain asymptomatic during the 7-to 17-daylong incubation period, after which symptoms develop, including fever, malaise, and head and body aches, followed by oropharyngeal lesions and skin rash 2 to 4 days later. Sloughing of oropharyngeal lesions and respiratory tract release discharge infectious viral particles into the air, perpetuating human-tohuman spread (14, 27, 52). The high mortality rate associated with smallpox results from the overwhelming toxemia leading to respiratory and/or cardiac failure. These observations indicate that infection involves viral entry and exit through the oropharyngeal-respiratory route and suggest that the airways may play a key role in the viral life cycle.Because of the risks of experiments using variola virus, the limitations and difficulties associated with studies of nonhuman animals, and insufficient clinical information from humans, much of our knowledge about the interaction between poxvirus and the host has come from studies using vaccinia virus and cultured cells. Vaccinia virus is the orthopoxvirus used for immunization against smallpox, and it is widely substituted for variola virus in the investigation of poxvirus biology (20,28,4...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Vermeer

McHugh

Rokhlina

et al. 2007

J Virol

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“…Hahon and Wilson demonstrated that infection of Macaca irus with high dose [5 × 10 5 PFU] fine particle (<5 µm) variola aerosols produced a disease that simulated human smallpox (Hahon and Wilson, 1960;Hahon, 1961). The initial site of virus replication was the lung, with subsequent appearance of virus in the nasopharynx and nares.…”

Section: Animal Modelsmentioning

confidence: 99%

“…However, emphasis on spread via large droplets may reduce the vigilance with which more difficult airborne precautions are maintained. High concentrations of variola in the lung during the incubation and prodromal periods in monkeys after simulated use of variola as a bioweapon (Hahon, 1961) may indicate that first generation cases after an attack with a concentrated aerosol may be more infectious than expected based on historical data. Moreover, because airborne precautions are not routine for all hospitalized patients, and because first generation cases will probably not be initially suspected to have smallpox, it is likely that they will not be placed on airborne precautions until well into their infectious period.…”

Section: Epidemiologic Evidencementioning

confidence: 99%

What was the primary mode of smallpox transmission? Implications for biodefense

Milton¹

2012

Front. Cell. Inf. Microbio.

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The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.

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“…In addition to MPV, other poxviruses also produce poxlike diseases in nonhuman primates. These include smallpox (6,13,36,58,59), Yaba tumor virus (10), Yaba-related virus (15,22,38,53,57), and molluscum contagiosum (27). Most species of monkeys are not very susceptible to experimental infection with smallpox virus (5,14,36,58).…”

Section: Classificationmentioning

confidence: 99%