Biologia

CLINICAL MICROBIOLOGY REVIEWS, Jan. 2007, p. 49–78
0893-8512/07/$08.00 0 doi:10.1128/CMR.00002-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vol. 20, No. 1

Role of Cell Culture for Virus Detection in the Age of Technology
Diane S. Leland1* and Christine C. Ginocchio2,3
Indiana University School of Medicine, Department of Pathology and LaboratoryMedicine, Indianapolis, Indiana1;
North Shore LIJ Health System Labs, Lake Success, New York2; and North Shore University Hospital,
Department of Laboratory Medicine, Manhasset, New York3

ination with antibiotics and clean-air equipment, and helped
decrease the use of experimental animals (55). Viruses reach
high titers when grown within susceptible cells, and culture
tubes are convenient tomanipulate.
Although virus isolation in cell cultures was employed by
research laboratories by the early 1960s, diagnostic services
were very limited, varying from laboratory to laboratory and
often not available at all, except in major medical centers.
However, by the early 1970s, diagnostic virology expanded
dramatically, largely because of the availability of highly purified reagents andcommercially prepared cell lines (71). The
types of cells that can be grown in vitro in flasks and test tubes
are many, providing living hosts that many human viruses can
infect. Cell cultures are more convenient and less expensive

INTRODUCTION
The discovery in the early 1900s that human cells could be
propagated in vitro provided virologists with an alternative to
embryonated eggs andlaboratory animals for in vitro isolation
of viruses. Cell cultures, which are derived from dispersed cells
taken from original tissue and disaggregated by enzymatic,
mechanical, or chemical means, provided large numbers of
cells suitable for virus isolation, facilitated control of contam-

* Corresponding author. Mailing address: Department of Pathology
and Laboratory Medicine, ClarianPathology Laboratory, Room
6027F, 350 W. 11th Street, Indianapolis, IN 46202. Phone: (317) 4916646. Fax: (317) 491-6649. E-mail: dleland@iupui.edu.
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INTRODUCTION .........................................................................................................................................................49
VIRUS ISOLATIONIN TRADITIONAL CELL CULTURES................................................................................50
NEWER CELL CULTURE FORMATS .....................................................................................................................55
CRYOPRESERVED CELL CULTURES...................................................................................................................55
CENTRIFUGATION-ENHANCED INOCULATION AND PRE-CPE DETECTION OF VIRUSES IN CELL
CULTURES ...........................................................................................................................................................56
VIRUS ISOLATION IN COCULTURED CELLS....................................................................................................57VIRUS ISOLATION IN TRANSGENIC CELL LINES...........................................................................................60
NONCULTURE METHODS COMPARED TO VIRUS ISOLATION IN CELL CULTURES..........................64
IF Methods................................................................................................................................................................64
Non-IF Methods ........................................................................................................................................................66
Molecular Methods...................................................................................................................................................68
APPLICATIONS OF VIRAL DIAGNOSTIC TECHNIQUES...