Abstract
Discussion and summary. The presence of interferon in dermal cells of vaccinia vaccinations of man is not unexpected since this substance has been detected in a variety of host systems infected with vaccinia virus(1-4). Interferon in vaccination crusts could be either a nonfunctional response to vaccinia virus multiplication or could serve to suppress virus multiplication until immune mechanisms are mobilized. Thus in man, as has been suggested in animal systems (12), interferon may be associated with recovery from infection with vaccinia virus.
The role of interferon in ameliorating the clinical course of smallpox is conjectural. However, several observations tend to support such a relationship. First, it has been found that vaccination with vaccinia virus shortly after exposure to smallpox virus results in a milder subsequent clinical course of smallpox(l3). These beneficial effects occur too soon after vaccination to be attributable to antibody production and may be due to interferon. Secondly, although variola virus can be isolated from both the upper respiratory tract and dermal crusts of patients with smallpox, it is believed that the respiratory tract virus produces the characteristic virulent disease, whereas it has been observed that dermal crust virus preparations produce a milder form of smallpox irrespective of route of inoculation(l4). These facts can be reconciled if one postulates the presence in dermal crusts of a factor other than virus which has virus inhibitory properties such as interferon, although the possibility does exist that such a factor may also be present in respiratory droplets. That occasional fatal cases of variolation smallpox occur may be due to the absence of interferon in a small percentage of crusts as was found in the present investigation with vaccinia dermal crusts. An alternative explanation for the relatively mild clinical course of variolation smallpox is that the variola virus becomes modified during its dermal passage (15). However, no differences between viruses derived from respiratory and dermal cells have been demonstrated.
Finally, special attention should be given to the experiments reported by Isaacs et a1 (16) who showed that the vaccinia vaccination reaction can be completely suppressed in man by prior subcutaneous administration od interferon. The close antigenic and structural relationships between variola and vaccinia viruses make it probable that virusinterferon relationships are also similar although it has been shown that virulent strains of a given virus type often induce less interferon (l7,18). If interferon is present in variola dermal crusts as it is in vaccinia crusts, then the inoculation of interferon together with variola virus in variolation could similarly temporarily suppress virus multiplication, permit host defense mechanisms to mobilize and result in a relatively benign clinical course of smallpox.
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