Mode of Parainfluenza Virus Transmission Determines the Dynamics of Primary Infection and Protection from Reinfection

Abstract

Little is known about how the mode of respiratory virus transmission determines the dynamics of primary infection and protection from reinfection. Using non-invasive imaging of murine parainfluenza virus 1 (Sendai virus) in living mice, we determined the frequency, timing, dynamics, and virulence of primary infection after contact and airborne transmission, as well as the tropism and magnitude of reinfection after subsequent challenge. Contact transmission of Sendai virus was 100% efficient, phenotypically uniform, initiated and grew to robust levels in the upper respiratory tract (URT), later spread to the lungs, grew to a lower level in the lungs than the URT, and protected from reinfection completely in the URT yet only partially in the lungs. Airborne transmission through 7.6-cm and 15.2-cm separations between donor and recipient mice was 86%–100% efficient. The dynamics of primary infection after airborne transmission varied between individual mice and included the following categories: (a) non-productive transmission, (b) tracheal dominant, (c) tracheal initiated yet respiratory disseminated, and (d) nasopharyngeal initiated yet respiratory disseminated. Any previous exposure to Sendai virus infection protected from mortality and severe morbidity after lethal challenge. Furthermore, a higher level of primary infection in a given respiratory tissue (nasopharynx, trachea, or lungs) was inversely correlated with the level of reinfection in that same tissue. Overall, the mode of transmission determined the dynamics and tropism of primary infection, which in turn governed the level of seroconversion and protection from reinfection. These data are the first description of the dynamics of respiratory virus infection and protection from reinfection throughout the respiratory tracts of living animals after airborne transmission. This work provides a basis for understanding parainfluenza virus transmission and protective immunity and for developing novel vaccines and non-pharmaceutical interventions.

Relationships among Dissemination of Primary Parainfluenza Virus Infection in the Respiratory Tract, Mucosal and Peripheral Immune Responses, and Protection from Reinfection: a Noninvasive Bioluminescence-Imaging Study

“…Working stocks of recombinant Enders strain Sendai viruses rSeV-luc(M-F*) and rSeV-luc(P-M) were generated and characterized in vitro and in vivo previously (16,24). In brief, the viruses were rescued by reverse genetics in LLC-MK2 cells, propagated twice in the allantoic cavities of 10-day-old embryonated eggs, plaque purified by LLC-MK2 cells, and confirmed to contain no mutations by reverse transcription-PCR (RT-PCR) and sequencing.…”

“…In vivo images were acquired with an Ivis charge-coupled-device (CCD) camera system (Xenogen Corp.) and analyzed with Living Image 4.2 software (Xenogen Corp.). Camera settings and image processing methods were described previously (16).…”

“…These viruses also reinfect people symptomatically throughout life (14), even in the absence of antigenic drift. While subversion of the host immune response may contribute to reinfection (2), it is also possible that anisotropic infections, such as those observed in smallpox infections (15), influence the magnitude and tissue tropism of both primary infection and protection from reinfection (16).…”

“…Wild-type Sendai virus and the nonattenuated reporter virus rSeV-luc(M-F*) have similar growth rates in cell culture and in the respiratory tracts of mice; moreover, both viruses induce similar levels of morbidity and mortality, T-cell infiltration into bronchoalveolar lavage fluid (BALF), cytokine profiles, and Sendai virus-specific antibody responses (24). Similar to HPIVs and wild-type Sendai virus (31)(32)(33), rSeV-luc(M-F*) is transmitted most efficiently by contact transmission but also by the shortrange airborne route (16).…”

“…Thus, there appears to be a separation of transmissibility and pathogenicity for Sendai virus in mice (24). Further use of the imaging system revealed that natural infections after short-range airborne transmission are anisotropic, initiating in either the nasopharynx or trachea before either remaining localized or disseminating throughout the respiratory tract (16). Moreover, the mode of transmission and tropism of primary infection were found to determine the extent of protection from reinfection.…”