Although capsids of herpes simplex virus were encountered within phagocytic vesicles, they were more commonly observed free within the cytoplasm. Stages in the release of virus from vesicles were not seen. There appeared to be five distinct steps in the process whereby the virus initiates infection: attachment, digestion of the viral envelope, digestion of the cell wall, passage of the capsid directly into the cytoplasm, and digestion of the capsid with release of the core. Antibody probably interferes with the first two stages. This paper describes and illustrates the probable manner in which herpes simplex virus (Herpesvirus hominis) initiates cellular infection. The three ensuing papers are concerned with the sequential stages of viral development, the effects of blocking DNA synthesis, and the antigenic alteration of host cell components. Since the initial examination of herpes simplex virus in thin sections (21, 22) a confusing nomenclature has arisen, including such descriptive terms as internal body, nucleoid, central body, internal membrane, peripheral coat, second membrane, single membrane form, naked particle, double membrane form, and complete virus. ["Nucleoid" was originally coined to describe the dense, eccentrically placed structure in immature forms of vaccinia and fowl pox viruses (23). It has become an unfortunate misnomer when applied to the dense cores characterictic of the majority of viruses.l Application of the negative staining technique, however, has now provided more precise information about the structure of the virus (33), which indicates that it consists of a core surrounded by a capsid. The capsid is icosahedral in shape and is composed of 162 capsomeres arranged in 5:3:2 axial symmetry. Capsids may or may not be enclosed within an envelope that is devoid of clearly defined subunits. Applying this nomenclature (19) to the appearance of the virus in thin sections, one can recognize a clearly defined core, a capsid (the first or inner membrane), and an envelope (the second or peripheral membrane). These terms will be used henceforth.

Stages in the direct penetration of adenovirus through the cell membrane are illustrated. Phagocytosis with rupture of the vacuole and release of virus into the cytoplasm may also account for entry of some particles. Uncoating by digestion within phagosomes was not observed. Rather, alteration of capsid and core occurred to virions free in the cytoplasm. Nucleoprotein released from virus close to the nucleus was transported to the nuclear matrix by a unique mechanism. These events were not prevented by puromycin and hence were not dependent upon the synthesis of new enzymes. They were, however, energy-dependent.