Results
Influenza Virus Does Not Transmit Readily Between Mice. We evaluated
the ability of the following to undergo transmission
between mice: the 1918 influenza virus, the mouse-adapted
WSN virus, a contemporary human influenza virus, a prototypical
human influenza virus isolated in 1968, and a highly
pathogenic H5N1 virus isolated from a human in 2004. Seven
mice were inoculated intranasally, and naı¨ve mice were subsequently
placed in the same cage with the inoculated animals.
Mice infected with 106 plaque-forming units (pfu) of 1918 or
WSN viruses exhibited severe illness, and none of the mice survived past day 8 postinoculation (p.i.) (experiment 1 in Table
1).Although infectious virus was detected in the upper and lower
respiratory tract of all H1N1 virus-inoculated animals, no virus
was detected in any of the tissues collected from the contact mice
on day 4 postcontact (p.c.), and convalescent sera collected from
the contact animals were negative for the presence of H1N1
hemagglutination-inhibiting antibodies. Mice infected with a
nonlethal dose (103 pfu) of 1918 virus exhibited less severe illness
and survived the infection but still presented mean lung titers of
5.6 log10 50% egg infectious dose (eID50)ml on day 4 p.i.
(experiment 2 in Table 1). The highly pathogenic human influenza
AVietnam120304 (H5N1) isolate, previously shown to
be lethal in mice (20), replicated to high titers in both the upper
and lower respiratory tract and induced severe clinical illness,
such as ruffled fur and listlessness during the first week of
infection, and caused death by day 8 p.i. The human influenza
AHong Kong81968 (H3N2) virus induced only minimal
clinical illness and weight loss and replicated to modest titers (4.2
log10 eID50ml) in the lung tissue. Examination of contact
animals housed with each virus-infected group again revealed a
lack of transmission among mice: Virus was not recovered from
any of the contact animals, nor did any of the contacts display
weight loss (not shown) or seroconvert (Table 1).