F0-containing noninfectious Sendai virus can initiate replication in mouse lungs but requires a relatively long incubation period

Abstract

The replication of LLC-MK2-grown noninfectious Sendai virus, containing exclusively fusion (F) glycoprotein precursors, was examined in the mouse lung to study the accessibility of virus inoculated intranasally to the virus activator present in the lung. When mice were intranasally inoculated with various doses of the virus after in vitro activation with trypsin, the 50% mouse infectious dose (MID50) was determined to be 0.7 cell-infectious units (CIU) per mouse, indicating that one infectious unit of Sendai virus is enough to initiate replication in the mouse lung and that the present experimental system is highly sensitive. On the other hand, in mice inoculated with virus not treated with trypsin, virus replication in the lung was recognized even in mice inoculated with samples containing no infectious virus, and the MID50 was determined to be 67.5 CIU per mouse (here, CIU were assayed after in vitro trypsin treatment). When mice were infected with 20 MID50 of trypsin-treated infectious and untreated noninfectious viruses (an approximately 100-fold greater amount of noninfectious virus than of infectious virus was used), the noninfectious virus was found to require 2 more days of incubation than the infectious virus, and many of the F proteins synthesized in the lungs of mice infected with the F0-containing virus were present in the cleaved form. In addition, the infection of mice with noninfectious virus was strongly suppressed by aprotinin, a serine protease inhibitor. These results indicate that Sendai virus can initiate replication in the mouse lung even with the F0-containing noninfectious virus and strongly suggest that this infection process is mediated by cleavage activation of the F0 proteins of inoculated viruses by a serine protease(s) present in the lumen of the mouse respiratory tract but that activation of the noninfectious virus is an inefficient process.