HCMV spread and cell tropism are determined by distinct virus populations.

Human cytomegalovirus (HCMV) can infect many different cell types
in vivo. Two gH/gL complexes are used for entry into cells.
gH/gL/pUL(128,130,131A) shows no selectivity for its host cell,
whereas formation of a gH/gL/gO complex only restricts the tropism
mainly to fibroblasts. Here, we describe that depending on the cell
type in which virus replication takes place, virus carrying the
gH/gL/pUL(128,130,131A) complex is either released or retained
cell-associated. We observed that virus spread in fibroblast
cultures was predominantly supernatant-driven, whereas spread in
endothelial cell (EC) cultures was predominantly focal. This was
due to properties of virus released from fibroblasts and EC.
Fibroblasts released virus which could infect both fibroblasts and
EC. In contrast, EC released virus which readily infected
fibroblasts, but was barely able to infect EC. The EC infection
capacities of virus released from fibroblasts or EC correlated with
respectively high or low amounts of gH/gL/pUL(128,130,131A) in
virus particles. Moreover, we found that focal spread in EC
cultures could be attributed to EC-tropic virus tightly associated
with EC and not released into the supernatant. Preincubation of
fibroblast-derived virus progeny with EC or beads coated with
pUL131A-specific antibodies depleted the fraction that could infect
EC, and left a fraction that could predominantly infect
fibroblasts. These data strongly suggest that HCMV progeny is
composed of distinct virus populations. EC specifically retain the
EC-tropic population, whereas fibroblasts release EC-tropic and non
EC-tropic virus. Our findings offer completely new views on how
HCMV spread may be controlled by its host cells.