The Pathogenesis of Pneumonitis Due to Murine Cytomegalovirus

Abstract

Virus replication and interstitial pneumonia were studied in BALB/c mice inoculated intranasally with murine cytomegalovirus (MCMV). In normal mice MCMV replicated in lung tissue but did not produce any consistent histologic abnormalities through day 21. The addition of a single dose of cyclophosphamide (0.20 mg/g) 24 hr after virus inoculation resulted in a slight increase in lung virus titers on day 10. No histologic abnormalities were noted before day 10. However, 22 or 32 virus-infected mice treated with a single dose of cyclophosphamide but only two of 26 simultaneously mock-infected, cyclophosphamide-treated mice developed severe interstitial pneumonia 10-14 days after inoculation. In contrast, animals given cyclophosphamide (0.05 mg/g) every five days after the initial dose developed a 10-fold increase in lung virus titer, but interstitial pneumonia was not observed. These data suggest that the interstitial pneumonitis seen with MCMV pulmonary infection may be immunologically mediated rather than the result of direct viral damage to the lung.

Comparison of the Pathogenesis of Murine Cytomegalovirus in Lung and Liver Following Intraperitoneal or Intratracheal Infection

“…infection may be influenced by differences in virus titres in the spleen. Our data are consistent with those of Shanley et al (1982), who reported similar virus titres in lung, liver and salivary gland of BALB/c mice following intranasal (i.n.) infection.…”

“…His results seem to be due to the particular strain of mice he used. Unfortunately, since this strain is no longer available the reason for their exceptional sensitivity to MCMV remains a mystery (Shanley et al, 1982).…”

“…Murine cytomegalovirus (MCMV) has been used extensively as an experimental model to study the pathogenesis of cytomegalovirus infections (for review, see Osborn, 1982), Because HCMV pneumonia is a serious problem for human transplant patients, several investigators have studied the effects of MCMV on the lung (Brody & Craighead, 1974;Brody 1978 ;Jordan, 1978;Rose et al, 1982;Shanley et al, 1982;Quinnan et al, 1982). The more recent of these studies have initiated infection via the respiratory route because epidemiology suggests that droplet transmission may frequently be the route of entry for human virus (Gold & Nankervis, 1976).…”

Host Genetic Factors Influence Murine Cytomegalovirus Lung Infection and Interstitial Pneumonitis

“…The virus has been maintained by serial passage in BALB/c mice and prepared as a 10~ (w/v) homogenate of salivary gland tissue. For these experiments, the virus was passed once in tissue culture using mouse embryo cells (MEC) and aliquots were prepared from clarified tissue culture supernatants (Shanley et al, 1982). The inoculum for mock-infected controls was prepared by heating the virus inocutum at 56 °C for 60 min to destroy viable MCMV.…”

“…In order to gain insight into the potential mechanisms operating in CMV interstitial pneumonitis, we have been evaluating a murine model of murine CMV (MCMV) interstitial pneumonia. We previously reported that BALB/c mice inoculated with MCMV and given a single dose of cyclophosphamide (CP) develop interstitial pneumonia not seen with MCMV or CP alone (Shanley et al, 1982). These studies also suggested that immunopathogenic factors contribute to the interstitial pneumonia in this model.…”