Influenza C Virus Infection in Rats

Abstract

Four-week-old rats (WKA/Hkm strain) were infected intranasally with the Ann Arbor/1/50 strain of influenza C virus and examined for clinical symptoms, virus replication, and serum antibody response. Although the animals showed no definite signs of illness, the virus replicated in the nose, and the hemagglutinationinhibiting (HI) and neutralizing antibodies were produced in their sera. When the inoculum sizes of 106.2 and 103.2 PFU were used, virus was recovered from nasal homogenates between days 1 and 10, and serum HI antibody became detectable by 10 days after infection. The rats infected with 101.2 PFU of the virus continued to shed virus until as late as day 20 without producing serum HI antibody. The amount of virus recovered from the nose was not affected significantly by either sex, age, or strain of the rat except that a slower virus growth was seen in the LE strain. It was also observed that the rats, previously inoculated with 103.2 PFU of the virus, showed no virus shedding when reinfected 7 weeks later but produced virus though in low titers when reinfected 50 to 55 weeks later. Virus was also recovered from rats once inoculated with 101.2 PFU of the virus when challenged 7 weeks later. Thus repeated infections characteristic of human influenza C can be produced in rats under the restricted conditions. Previous seroepidemiological studies revealed that influenza C virus is widely distributed throughout the world and that primary infection occurs early in life (5,9,11,12). However, clinical features of infection with this virus have remained obscure until recently since outbreaks of illness caused by influenza C virus alone have rarely been documented and the virus has been isolated only occasionally. In 1981, Katagiri et al (6) first succeeded in observing a genuine outbreak of influenza C and revealed that the disease was characterized by 2-to 3-day fever of 38-40 C and long-lasting (3 weeks) nasal discharge. The authors also described that the patients shed virus for a long period (more than 9 days) and that three of 19 patients were cases of reinfection. A long-lasting virus shedding as well as the repeated infections appears to play an important role in the transmission and maintenance of influenza C virus in the human population.

Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses

“…The findings indicate that a natural capability of inducing random mutations in the influenza C virus is inferior to the capability of the other two viruses. Possible explanations for this could be a slow replication cycle [56,57], low yield of progeny virus in infected individuals [58], and high fidelity of viral RNA polymerase (no published evidence to our knowledge) of the influenza C virus.…”

Protective effect of serum antibody on respiratory infection of influenza C virus in rats

“…We observed previously that influenza C virus did not replicate in the lung when rats were infected by the intranasal route [26]. As seen in Fig.…”

“…It was observed previously that blood contamination was detected, though at a low level, in the nasal homogenates even when the tissues were extensively washed by the perfusion procedure prior to homogenization [26], raising the possibility that in vitro neutralization may occur during tissue homogenization if animals have a serum neutralizing antibody at high titers. In contrast, blood contamination was undetectable in the nasal wash specimens obtained according to the procedures described in Materials and methods (see Table 1).…”

“…We reported previously that the growth of influenza C virus in the nose was greatly restricted when rats were reinfected 7 to 55 weeks after the first exposure to the virus [26]. Many of these resistant animals were shown to possess extremely low titers (__< 1"10) of serum neutralizing antibody.…”

Host Range, Biology, and Species Specificity of Seven-Segmented Influenza Viruses—A Comparative Review on Influenza C and D

“…The intranasal inoculation of four-week-old rats with C/Ann Arbor/1/50 of ICV showed no clinical signs; however, it caused nasal shedding for 10-20 days, and seroconversion [109]. The viral shedding peaked at 24 hpi, and stayed until 5 dpi [109]. Administration of convalescent sera before ICV infection rendered complete resistance to lung infection in rats [110].…”