Experimental influenza causes a non-permissive viral infection of brain, liver and muscle

To determine whether some constitutional symptoms of influenza, such as headache, myalgia and nausea, could represent a viral infection of brain, muscle, and liver, we inoculated juvenile Balb/c mice intranasally with 103 plaque forming units of influenza B/Lee virus. Blood, brain, liver, skeletal muscle, and lung tissues were removed aseptically and assayed for infectivity by a plaque assay, viral RNA by reverse transcriptase-polymerase chain reaction (RT - PCR), viral antigen by immunoperoxidase staining, and histologic changes by light microscopy. Mice became ill 2 - 3 days post inoculation (PI). A productive viral infection of the lungs developed from days 1 - 8 with maxima of virus titers, pneumonia, and the number of immunoperoxidase staining lung cells occurring on days 2 - 6 PI. Virus isolation from blood was rare and viral RNA was detected intermittently in blood by RT - PCR. In many animals, a non-permissive or abortive infection of brain occurred from days 1 - 8 and peaked on days 3 - 4 PI. Viral RNA was detected in brain tissue and viral antigen was seen in cerebral endothelial cells but infectious virus was rarely isolated from brain. In liver, viral RNA was detected and viral antigen was seen occasionally in hepatocytes. In skeletal muscle, viral RNA was detected but neither infectious virus nor viral antigen was seen. A correlation existed between the severity of the illness, pneumonia, lung virus titer, viral antigen in lung cells, and extent of a non-permissive viral infection of brain and liver but not muscle. These studies demonstrate that following intranasal infection of influenza virus in mice, a viral pneumonia develops with subsequent intermittent viremia and non-permissive or abortive infection of brain, liver and muscle.