Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains

Abstract

Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection.

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

“…with a relatively high dose (7,000 PFU) and high volume (30 l), which initiates infection throughout the respiratory tract (36). Inoculations with relatively high doses (Ն200 PFU) and high volumes (20 to 50 l) are common in Sendai virus pathogenesis and immunological studies (37,(39)(40)(41)(42)(43)(44). High-dose, high-volume inoculation is valuable in inducing LRT pathogenesis, which is mostly observed clinically as 6 PFU of rSeV-luc(M-F*) in 30 l, and mice were monitored for 21 days for changes in body weight (A) and survival (B).…”

Pneumonia virus of mice: severe respiratory infection in a natural host

“…Since that time, the PVM strain 15 has reportedly undergone tissue culture passage, thus losing some of its pathogenicity in vivo, although the extent to which this is so, and in which specific isolates, remains uncertain. A second strain, PVM strain J3666, also developed at the Rockefeller University, has been reportedly maintained in mice with minimal tissue-culture passage, and has recently been shown to be highly pathogenic in nearly all inbred strains of mice [13]. In our hands, PVM strain 15 from Dr. Andrew Easton's laboratory (PVM strain 15 Warwick) is highly attenuated and elicits a minimal inflammatory response in the highly susceptible BALB/c strain of mice [14].…”

Human Genetic Factors and Respiratory Syncytial Virus Disease Severity

“…Alternative smallanimal models would include rodent models that use Sendai virus or pneumonitis virus, the latter virus having significant similarity with the RSV virus and yet causing severe bronchiolitis in mice (110). Significant variabilities in susceptibilities to these two viruses among different inbred mouse strains have been reported, which could be subjected to a forward genetic analysis (4,34).…”