Comparison of the pathogenesis of the highly passaged MCMV Smith strain with that of the low passaged MCMV HaNa1 isolate in BALB/c mice upon oronasal inoculation.

Shunchuan Zhang,Hans J Nauwynck,Jun Xiang,Jan Van Doorsselaere

doi:10.1186/s13567-015-0228-6

Shunchuan Zhang, Hans J Nauwynck + Show 2 more

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https://doi.org/10.1186/s13567-015-0228-6

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Abstract

Murine cytomegalovirus (MCMV) Smith strain is widely used in mouse models to study HCMV infections. Due to high serial passages, MCMV Smith has acquired genetic and biological changes. Therefore, a low passaged strain would be more relevant to develop mouse models. Here, the pathogenesis of an infection with MCMV Smith was compared with that of an infection with a low passaged Belgian MCMV isolate HaNa1 in BALB/c adult mice following oronasal inoculation with either a low (104 TCID50/mouse) or high (106 TCID50/mouse) inoculation dose. Both strains were mainly replicating in nasal mucosa and submandibular glands for one to two months. In nasal mucosa, MCMV was detected earlier and longer (1–49 days post inoculation (dpi)) and reached higher titers with the high inoculation dose compared to the low inoculation dose (14–35 dpi). In submandibular glands, a similar finding was observed (high dose: 7–49 dpi; low dose: 14–42 dpi). In lungs, both strains showed a restricted replication. In spleen, liver and kidneys, only the Smith strain established a productive infection. The infected cells were identified as olfactory neurons and sustentacular cells in olfactory epithelium, macrophages and dendritic cells in NALT, acinar cells in submandibular glands, and macrophages and epithelial cells in lungs for both strains. Antibody analysis demonstrated for both strains that IgG2a was the main detectable antibody subclass. Overall, our results show that significant phenotypic differences exist between the two strains. MCMV HaNa1 has been shown to be interesting for use in mouse models in order to get better insights for HCMV infections in immunocompetent humans.

Highlights

Human cytomegalovirus (HCMV), known as human herpesvirus 5 (HHV-5), is the prototype member of the Betaherpesvirinae within the family of the Herpesviridae
Virus titers in tissues Low dose After oronasal inoculation of 104 TCID50 per mouse, MCMV HaNa1 was detected in the nasal mucosa from 14 till 35 dpi with the highest mean virus titer of 103.53 TCID50/g at 14 dpi, in submandibular glands from 14 till 35 dpi with the highest mean virus titer of 104.93 TCID50/g at 21 dpi (Figure 2), and in lungs, plasma, and saliva only at one time point (14 (n = 1), 21 (n = 2) and 28 (n = 1) dpi, respectively)
MCMV Smith was detected in the nasal mucosa from 14 till 35 dpi and in submandibular glands from 14 till 42 dpi with the highest mean virus titer in the nasal mucosa (103.01 TCID50/g) at 14 dpi and in the submandibular glands (103.72 TCID50/g) at 17 dpi (Figure 2)

Summary

Introduction

Human cytomegalovirus (HCMV), known as human herpesvirus 5 (HHV-5), is the prototype member of the Betaherpesvirinae within the family of the Herpesviridae. It is an ubiquitous virus with a worldwide distribution [1]. Due to the strict species-specificity of HCMV, it is not possible to study this virus in experimental animals. It is necessary to set up animal models for the study of HCMV. A number of CMV infections in various animal species have been utilized for modeling HCMV infection. The mouse model with MCMV is the most commonly and widely used animal model for HCMV study, due to the following reasons: (1) MCMV shares many features with HCMV [4], (2) the genomes of mice and MCMV are fully sequenced [14,15] and (3)

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