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2015 ; 56
(1
): 472-7
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Ultrastructure of adenovirus keratitis
#MMPMID25564451
Mukherjee S
; Zhou X
; Rajaiya J
; Chodosh J
Invest Ophthalmol Vis Sci
2015[Jan]; 56
(1
): 472-7
PMID25564451
show ga
PURPOSE: We determined the ultrastructure of mouse adenovirus keratitis, a model
for human adenovirus keratitis. METHODS: Adenovirus keratitis was induced in
C57Bl/6j mice by intrastromal injection of human adenovirus species D type 37
(HAdV-D37) with a heat-pulled, glass, micropipette needle under compressed air.
At select time points after infection, mice were euthanized and their corneas
removed, fixed, and sectioned at 70-nm thickness for electron microscopy.
RESULTS: Injection of HAdV-D37 into the mouse corneal stroma placed virus
predominantly in the pericellular corneal stromal matrix. Virus was seen bound to
and entering stromal cells at 1 and 2 hours after infection, respectively. Cell
membrane transit by virus was seen to involve two distinct structures resembling
caveolae and macropinosomes. However, later during infection intracellular virus
was not seen within membrane-bound organelles. By 8 hours after infection,
intracellular virus had accumulated into densely packed, perinuclear arrays.
Virus disassembly was not obvious at any time point after infection. Infiltrating
neutrophils seen by one day after infection had engulfed degraded stromal cells
by 4 days after infection. CONCLUSIONS: By transmission electron microscopy,
injected HAdV-D37 readily enters stromal cells in the C57Bl/6j mouse cornea and
induces stromal inflammation, as was shown previously by light microscopy.
However, electron microscopy also revealed dense, static arrays of
intracytoplasmic virus, suggesting a block in viral capsid disassembly and viral
DNA nuclear entry. These findings may explain why human adenoviruses do not
replicate in the mouse corneal stroma.