Cytopathic effect (CPE) of Viruses: Types with Examples

Visible morphological changes in cell cultures caused by viral infections are called cytopathic effects (CPE). The degree of visible changes to cells caused by viral infection varies with the type of virus, type of host cells, the multiplicity of infection (MOI), and other factors.

HeLa cell lines infected with poliovirus
HeLa cell lines infected with poliovirus
(From top left, normal cells, 4 hours, 8 hours and 12 hours after infections)

Some viruses cause very little or no CPE in the cells of their natural host, while others cause complete and rapid destruction of the cell monolayer after infection. Cell line supporting virus replication, the time required to produce CPE, and the microscopic appearance of the CPEs may be sufficiently characteristic to allow the provisional identification of an unknown virus.

Viruses have distinct CPEs, just as colonies of bacteria on agar plates have unique morphologies.

Syncytia cytopathic effects

Some CPE can be readily observed in unfixed, unstained cells under the low power of the light microscope. Still, several types of CPE are distinguishable in living cultures, thus requiring fixation and staining of the cells. Cell cultures are stained with hematoxylin, a basic dye, and eosin, an acidic dye. 

Recognizing CPE and using it as a diagnostic tool requires much experience examining both stained and unstained cultures of many cell types. Uninfected cells should always be run as a control to distinguish age-related changes in infected cells from the cytopathic effects.

Types of Cytopathic effects

Summary of Cytopathic effect(s) of common, clinically encountered viruses

Cytopathic effect(s)Virus(es)
Morphological alternations
Nuclear shrinking (pyknosis), proliferation of membranePicornaviruses
The proliferation of nuclear membraneAlphaviruses, herpesviruses
Vacuoles in cytoplasmPolyomaviruses, papillomaviruses
Syncytium formation (cell fusion)Paramyxoviruses, coronaviruses
Margination and breaking of chromosomesHerpesviruses
Rounding up and detachment of cultured cellsHerpesviruses, rhabdoviruses, adenoviruses, picornaviruses
Inclusion bodies
Virions in nucleusAdenoviruses
Virions in the cytoplasm (Negri bodies)Rabies virus
“Factories” in the cytoplasm (Guarnieri bodies)Poxviruses
Clumps of ribosomes in virionsArenaviruses
Clumps of chromatin in the nucleusHerpesviruses


It is the most severe form of CPE. All cells in the monolayer rapidly shrink, become dense (pyknosis), and detach from the glass within 72 hours. This CPE is typical of most enteroviruses.

Cytopathic effect HSV

Subtotal destruction

It consists of detachment (death) of some but not all of the cells in the monolayer, which can be observed using the 20X objective. Some togaviruses (alphaviruses), some picornaviruses, and some paramyxoviruses may cause this type of CPE.

Focal degeneration

Instead of causing generalized cell monolayer destruction, some viruses produce localized areas (foci) of infection.  Cells become enlarged, rounded, and refractile, eventually detaching from the growth surface, leaving cleared areas surrounded by rounded-up cells as the infection spreads concentrically. Focal degeneration is characteristic of the herpesviruses and poxviruses.

Swelling and clumping

Infected cells greatly enlarge and clump together in “grape-like” clusters. For example, adenoviruses.

Foamy degeneration (vacuolization)

Severa virus families produce large and/or numerous cytoplasmic vacuoles.  Vacuolation is visible only after staining. Retroviruses, paramyxoviruses, and flaviviruses may cause vacuolization.

Syncytia formation
Syncytia formation

Cell fusion (syncytium or polykaryon formation) 

It involves the fusion of the plasma membranes of four or more cells to produce an enlarged cell with four or more nuclei.  Some paramyxoviruses; and herpesviruses may produce syncytia. Syncytia are much easier to observe after staining.

Inclusion bodies

These are areas of altered staining in cells that cannot be seen in live cell cultures. Depending on the causative virus, these inclusions may be single or multiple, large or small, round or irregularly shaped, intranuclear or intracytoplasmic, eosinophilic (pink staining), or basophilic (blue-purple staining).

Before, virologists used to rely on cytopathic effects to identify viruses. The reliance has decreased substantially due to a rise in nucleic acid amplification tests such as polymerase chain reaction (PCR), which is faster and more specific.

References and further readings

  1. Suchman, E., & Blair, C. (2007, September 29). Cytopathic Effects of Viruses Protocols.
  2. Tille, P. (2017). Bailey & Scott’s Diagnostic Microbiology (14 edition). Mosby.

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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