ABSTRACT
The family Picornaviridae comprises four genera, namely, rhinovirus, enterovirus, cardiovirus, and aphthovirus. 1 Of these, the first two are of importance in human disease.
Rhinoviruses tend to have particular cultural requirements relating to temperature of incubation and to composition of nutrient medium. 2 Some strains show preference for certain human or monkey cells;-'· 6 others are noncytopathic and require an interference test to reveal their presence. '· 8 Further information can be found in the review monograph by Tyrrell. 9
It is generally agreed that the site of picornavirus replication is in the cytoplasm, where it is marked by the appearance of a large round paranuclear zone which displaces and compresses the nucleus (Figures 12 and 13). * This area is hyaline and usually stains lightly with eosin. It is surrounded by denser cytoplasm in which basophilic bodies may be found (Figure 14) as noted by several early investigators. 14 . 17 This zone is sometimes referred to as an inclusion body, which it undoubtedly is; but its relative lack of staining capacity makes the term less appropriate for it than for most other inclusions. Picornavirus-infected cells may also have long cytoplasmic processes (Figure 15). Eventually the cells round up, become detached, and lyse through rupture of the cytoplasmic membrane, for which a cytotoxic double-stranded RNA viral product may be responsible. 1
In their historic study on the cultivation of poliovirus, Robbins et a!. 18 observed that in sectioned fragments of infected tissue there was loss of typical staining properties together with nuclear pyknosis and disintegration of the cells. Barski and his colleagues in Paris then reported the sequence of cytoplasmic changes in poliovirus-infected cells as seen by both direct and phase contrast light microscopy. 19 · 20 The appearance of small eosinophilic nuclear inclusions as early as 4 hr after infection with poliovirus was noted by Beale and his co-workers 21 and by Reissig et al., 15 but Mayor22 failed to detect viral antigen in such inclusions. Reports have appeared in the literature23 • 26 concerning the presence of virus-like particles in the nuclei of picornavirus-infected cells, but such structures have not been consistently observed, and the main replicative cycle appears to take place in the cytoplasm. 27 · 28 Cells enucleated with cytochalasin B and subsequently infected with poliovirus can maintain the whole cycle; but the nucleus may influence viral growth, because enucleated cells support replication less efficiently than do cells with nuclei. 29 · 30 Very early structural changes in the nuclei of poliovirusinfected cells have been noted, 31 but the virus inhibits synthesis of cellular RNA and protein, and the changes may in part be due to this. It has been suggested, however,
athology
thatmostofthemorphologicalchangescausedbypicornavirusesmaybeduetothe directactionofviralcomponentsratherthantotheinhibitionofcellular metabolism.3 2.3 3Thesimilaritybetweenearlyultrastructuralnucleolarchangescaused bycoxsackievirusA9andthoseproducedbyactinomycinDinpatasmonkeykidney cellswasnotedbyWeissandMeyer.34InbothinstancesinterferencewithcellularRNA metabolismmaybemanifestedinthesameway.Distinctivenucleolardispersionis seenincellsinfectedwithcertainsimianpicornavirusessuchasSV44(figure16). Thuswhilethemaincytopathiceffectisseeninthecytoplasm,lessobviouschanges occurinthenucleusaswell.
