Broadening the tissue tropism often increases the virulence. For example, poliovirus normally replicates in the guts and causes minor febrile illnesses. In rare cases (1%) the virus invades neurons and causes paralysis. But are there any cases that broadening the tissue tropism decreases the virulence? Imagine that we have two strains. One specifically infects the upper respiratory tract while the other specifically infects the lungs. The first strain is easily transmissible but very rarely fatal (few upper respiratory infections kill people as far as I know), while the second strain is difficult to transmit but highly lethal. Now imagine what will happen if there is another strain which can infect both the upper respiratory tract and the lungs. It’s intuitive that the new strain will combine the high transmissibility and high lethality. However, infection of the upper respiratory tract does little help to kill the patients, but can alert the immune system to neutralize the infection in the more critical part (lungs) especially if the virus invades the upper respiratory tract first. This is just my thought experiment. Are there any papers supporting this hypothesis?