In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques.
The global increase in measles vaccination has resulted in a significant reduction of measles mortality. The standard route of administration for the live-attenuated measles virus (MV) vaccine is subcutaneous injection, although alternative needle-free routes, including aerosol delivery, are under investigation. In vitro, attenuated MV has a much wider tropism than clinical isolates, as it can use both CD46 and CD150 as cellular receptors. To compare the in vivo tropism of attenuated and pathogenic MV, we infected cynomolgus macaques with pathogenic or attenuated recombinant MV expressing enhanced green fluorescent protein (GFP) (strains IC323 and Edmonston, respectively) via the intratracheal or aerosol route. Surprisingly, viral loads and cellular tropism in the lungs were similar for the two viruses regardless of the route of administration, and CD11c-positive cells were identified as the major target population. However, only the pathogenic MV caused significant viremia, which resulted in massive virus replication in B and T lymphocytes in lymphoid tissues and viral dissemination to the skin and the submucosa of respiratory epithelia. Attenuated MV was rarely detected in lymphoid tissues, and when it was, only in isolated infected cells. Following aerosol inhalation, attenuated MV was detected at early time points in the upper respiratory tract, suggesting local virus replication. This contrasts with pathogenic MV, which invaded the upper respiratory tract only after the onset of viremia. This study shows that despite in vitro differences, attenuated and pathogenic MV show highly similar in vivo tropism in the lungs. However, systemic spread of attenuated MV is restricted.
de Vries
Rory D
RD
Department of Virology, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, Netherlands.
Lemon
Ken
K
Ludlow
Martin
M
McQuaid
Stephen
S
Yüksel
Selma
S
van Amerongen
Geert
G
Rennick
Linda J
LJ
Rima
Bert K
BK
Osterhaus
Albert D M E
AD
de Swart
Rik L
RL
Duprex
W Paul
WP
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry / Q000821:virology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000821:virology; D008252:Macaca fascicularis; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000821:virology; D013194:Staining and Labeling / Q000379:methods; D013601:T-Lymphocytes / Q000821:virology; D019562:Viral Load; D056189:Viral Tropism; D014766:Viremia
D039521:CD11c Antigen; D049452:Green Fluorescent Proteins