A mutant influenza virus, A/NWS-Mvi, grows well in the presence of exogenou
s sialidase activity sufficient to remove all cell surface sialic acids. Re
lated wild-type viruses grow very poorly under these conditions, although m
utant and wild-type viruses bind to desialylated cells with similar efficie
ncy and show similar reduction of binding to sialidase-treated cells compar
ed to native cells. Here we examine entry, transcription, translation, and
RNA replication and find that, although the viruses appear to utilize the s
ame entry pathway, the mutant NWS-Mvi transcribes and replicates RNA to hig
her levels than the wild-type strains. The kinetics of replication in multi
-cycle infection show that this enhancement of RNA synthesis facilitates gr
owth where entry is restricted. The hemagglutinin (HA) protein of NWS-Mvi l
yses red blood cells 0.1 pH unit higher than wild-type viruses. This higher
fusion pH may allow more efficient release of nucleocapsids from endosomes
and contribute to the enhanced RNA synthesis. The efficient RNA synthesis
assists virus survival at low inocula or under stringent growth conditions,
such as the presence of antiviral agents. NWS-Mvi induces apoptosis in inf
ected cells more readily than wild-type viruses, apparently as a consequenc
e of enhanced production of viral mRNA. Since growth of NWS-Mvi is more eff
icient, apoptosis may play a positive role in viral replication by removing
cells that have already been infected from those capable of making more vi
rus. (C) 2001 Elsevier Science B.V. All rights reserved.