Characterization of the Infectious Unit for Man of Two Respiratory Viruses 1

Abstract

We have previously reported 50% human infectious doses (HID₅₀) of adenovirus, type 4 (adeno 4), and Coxsackie virus A, type 21 (A21) (1, 2). The HID₅₀) were determined in normal volunteers and expressed as 50% tissue culture infectious doses (TCID₅₀) using the most sensitive assay system available for each virus. Determinations of HID₅₀ were made for each virus with two different inoculation methods: nasal instillation of a small volume of virus suspension, which deposits entirely in the nasopharynx; and inhalation of a small particle aerosol, which deposits primarily in the lower respiratory tract. Adeno 4 was more infectious in small particle aerosol than in nasal drops; whereas the reverse was true for A21. While these data suggest important biologic differences between viruses, they do not provide absolute quantitation of infectious units and since the sensitivity of the respective assay systems is not known, they do not allow quantitative comparisons between viruses.

In order to characterize the infectious unit of these respiratory viruses for man, and to provide data with which comparisons could be made between viruses, we made electron microscopic counts of viral particulates and numbers of virions in particulates in the virus suspensions of adeno 4 and A21 which were used for volunteer inoculations. In the present report these data are presented and compared to the previous data on infectivity of the virus suspensions for man and for tissue culture.

Methods and Materials. Virus. The strains used in these studies were obtained from Marine recruits with acute respiratory disease. The adeno 4 volunteer inoculum (strain 78650) had been passaged once in human embryonic kidney tissue cultures (HEK). The harvest was frozen and thawed once, pooled, centrifuged at 1000g for 20 min, and filtered through 800 μg membrane filters (Millipore).