Interferon, nonspecific inflammation, and probably pyrexia play a role in limiting infection during the early stages. Infection induces humoral and cellular immune responses to naturally released virions and to viral antigens on the surface of virus-infected cells. In some cases the reservoir is known and distributed worldwide, as in the case of ovine and bovine parapoxviruses. Human infection with these viruses is an occupational hazard of those working with the infected reservoir hosts. Monkeypox is restricted to West Africa, and squirrels are more important as reservoir hosts than monkeys.
Bovine cowpox is rare, and the domestic cat is the most commonly reported host.
Conclusive information about the reservoir host of cowpox virus is lacking, but it is probably small wild rodents. Cases occur without known contact with cats or cattle, and indirect spread via barbed wire or brambles is possible. Parapox and cowpox infections rarely, if ever, spread from person to person. There is increasing evidence, however, that sexual transmission of molluscum is important. Vaccinia virus is traditionally regarded as a laboratory virus with no natural reservoir.