The Infectious Dose of Variola (Smallpox) Virus

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Abstract
Quantitative estimation of an individual's risk of infection due to airborne pathogens requires knowledge of the pathogen's infectious dose, in addition to estimates of the pathogen's airborne concentration and the person's exposure duration. Based on our review of the published literature on poxvirus infection, we conclude that the infectious dose of variola (smallpox) virus is likely one virus particle and that infection can be initiated in either the upper respiratory tract or pulmonary region. Studies of airborne transmission of poxvirus in monkeys and rabbits show that primary infection can occur in both regions of the respiratory tract. A quantitative study of poxvirus inhalation transmission in rabbits indicates that the deposition of one pock-forming unit (PFU) carried on respirable particles can cause infection. Findings in both in vitro and in vivo studies of the number of virus particles comprising a PFU are consistent with a “one-hit” phenomenon—namely, the cellular uptake of just one virus particle can lead to infection of a cell or an area of cell growth, creating a pock (an infected area of cells). Variability in virulence among different virus strains may involve differences in the probability of infection per virus particle, where a highly virulent strain has a probability close to one of successful infection for each virus particle. In an analogous manner, variability in susceptibility to the same virus strain among different hosts may involve differences in the probability of infection per virus particle across different hosts.