The vegetative stage of development of the human smallpox virus is described as being comprised of four successive periods: "without membrane" period; "open-cavity" period; "single-cavity" period; and "double-cavity" period. This classification is based on the organization of the virus membranes. This paper presents a description of the changes in virus structure during each period. It shows the strict sequence of morphological continuity and succession of differentiation of viral components. The most important stage of the development, the differentiation of virus nucleoid, takes place in the virus cavity morphologically isolated from the cellular milieu and limited originally by the external membrane of the virus and then by the second one, the primary membrane of the nucleoid. Osmiophilic fibrils 20 to 25 A wide, which fill the cavity of a mature nucleoid, become clearly evident after staining with uranyl acetate and are revealed only at the end of the last or double-cavity period. The main features of the developmental cycle of human smallpox virus may probably be characteristic of certain other groups of viruses.

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