Download Systemic dissemination of MCMV HaNa1 via non

Systemic dissemination of MCMV HaNa1 via non-productively
infected leukocytes between nose, lymphoid organs and salivary
glands upon oronasal exposure
Shunchuan Zhang†, Jun Xiang†, Lowiese Desmarets, Hans Nauwynck (†contributed equally)
Laboratory of Virology, Department of Virology, Parasitology, and Immunology, Faculty of
Veterinary Medicine, Ghent University, Merelbeke, Belgium
Abstract
The oronasal route is the most common way for infection of cytomegaloviruses (CMVs) in
mammals, but it remains unclear how an oronasal exposure results in infection and subsequent
shedding. To address this issue, BALB/c female mice were oronasally inoculated with the low
passaged murine cytomegalovirus (MCMV) HaNa1 isolate. Virus titration showed infectious virus
replication in the nasal mucosa from 1 dpi until the end of the experiment (14 dpi), in the lungs from
5 until 14 dpi, and in the submandibular glands from 7 until 14 dpi. Co-culture assay showed that
cell-associated virus was detected in the nasopharynx-associated lymphoid tissues (NALT) at 1 dpi,
in the submandibular lymph nodes and deep cervical lymph nodes at 3 dpi, in the spleen at 5 dpi,
and in the mediastinal lymph nodes and peripheral blood mononuclear cells (PBMC) at 7 dpi. In
conclusion, the present study shows that upon oronasal exposure, MCMV HaNa1 first enters the
nasal mucosa and NALT, from where the virus disseminates via the draining lymphatic system to
the spleen and lungs. A subsequent cell-associated viremia carries the virus from the spleen to
submandibular glands, where a second replication is started.