The spread and persistence of influenza viruses in normal and cyclophosphamide‐treated mice

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Abstract
The persistence and extrapulmonary spread of three strains of influenza virus, the mouse neuro‐adapted A/NWS virus, the wild‐type strain A/Victoria/75, and a recombinant virus RIT4050, bearing surface antigens derived from A/ Victoria/75, were studied in both normal and cyclophosphamide‐treated CBA mice following either intranasal or intracerebral inoculation. All three viruses showed increased lethality in mice in the presence of cyclophosphamide but exhibited distinctive patterns of replication and spread. The recombinant virus RIT4050 showed a reduced ability to replicate, persist, and spread in CBA mice compared to either A/NWS or A/Victoria/7 5 viruses, and in general, the A/NWS virus persisted to a greater extent than the A/Victoria/75 virus in both normal and treated mice. However, in the presence of cyclophosphamide, no extrapulmonary spread of A/NWS virus was observed. The reasons for the differences are discussed.