ABSTRACT
A model of influenza transmission has been established in ferrets in which wild-type influenza infection in a donor ferret can be transmitted sequentially to other ferrets. We have studied the transmission in ferrets of a clinical isolate of A/Sydney/5/97 (H3N2) carrying the neuraminidase 292K mutation compared with the corresponding wild-type virus from the same subject. Donor ferrets (n=four per group) were inoculated intranasally with mutant or wild-type virus and each housed with three naïve contact ferrets. All donor ferrets inoculated with wildtype virus were productively infected and transmitted virus to all 12 contacts, who in turn had high viral titres in their nasal washes. In contrast, only two of the donor ferrets inoculated with mutant virus were productively infected. There was little or no evidence that the two infected donor animals transmitted mutant virus to their contact animals. This ferret model has demonstrated that the mutant influenza virus with lysine at position 292 of the neuraminidase is of reduced infectivity and does not transmit under conditions in which the wild-type virus with arginine at position 292 readily transmits.
Subject(s)
Ferrets/virology , Influenza A virus/enzymology , Neuraminidase/genetics , Orthomyxoviridae Infections/transmission , Animals , DNA, Viral , Disease Models, Animal , Disease Transmission, Infectious , Fever , Influenza A virus/genetics , Male , Mutation , Nasal Lavage Fluid/virology , Sequence Analysis, DNA , Viral LoadABSTRACT
Ferrets were used as an animal model to study whether controlled transmission of type A influenza is similar to human transmission when sequence changes in HA1 are used as the outcome. Ferrets were infected initially with A/Sydney/5/97 (H3N2) or A/LA/1/87 (H3N2) intranasally, and transmission chains were established by housing infected ferrets with noninfected ferrets with no influenza antibody titer against the infecting virus. Ferrets infected with A/Sydney were seronegative for A/Sydney and A/LA; ferrets infected with A/LA were seronegative for A/LA but had hemagglutination inhibition titers against A/Sydney. Titers of naturally transmitted influenza were higher than those after direct intranasal infection, but lymphocyte counts from nasal washes diminished with transmission. Ferrets infected with A/LA had 2 amino acid differences in HA1 after transmission through 5 ferret cohorts, but those infected with A/Sydney had none. The results show the value of the ferret model. A/LA resembled the transmission of influenza in humans when under antibody pressure.
