Outcome of influenza infection: effect of site of initial infection and heterotypic immunity.

An infection established throughout the total respiratory tract of mice with a highly lung adapted influenza virus (H0N1) led to death from viral pneumonia. The 50% lethal dose (LD(50)) was approximately the same as the 50% infectious dose (ID(50)). An infection with the same virus initiated in the nasal mucosa spread to the trachea and lungs over a 3- to 5-day period but was not lethal except at very high infecting doses. The LD(50) was 30,000 times the ID(50). Mice that had recovered from a prior infection with A/PC/73(H3N2) demonstrated enhanced recovery (heterotypic immunity) when challenged with A/PR/8/34(H0N1). Heterotypically immune mice infected while anesthetized with this potentially lethal virus stopped shedding virus from the nose, trachea, and lungs by day 7 and recovered. Heterotypically immune mice, infected awake, stopped shedding virus from the nose by day 5, and, in fact, the virus did not spread to the trachea or lungs. Thus, some of the variation in the severity of influenza infections may be explained by two factors: the site of initial infection and previous infection with heterotypic influenza virus.