Cytopathic Effect in Herpes Simplex Virus Culture
The characteristic cytopathic effect (CPE) expected in viral culture for this patient with genital herpes would show ballooning of infected cells with multinucleation and intranuclear inclusion bodies, typically appearing within 24-72 hours after inoculation.
Viral Culture Findings in HSV Infection
HSV viral culture remains a cornerstone diagnostic method for herpes infections, particularly when PCR is unavailable. When examining the cytopathic effects in cell culture:
- Timing of CPE appearance: The characteristic cytopathic effect generally appears within 24-72 hours, but may take up to five days 1
- Early changes: As early as 4 hours post-infection, stereological studies show approximately 53% increase in nuclear volume and 46% increase in cell volume compared to uninfected cells 2
- Cellular morphology:
- Ballooning/enlargement of infected cells
- Formation of multinucleated giant cells (syncytia), which becomes particularly remarkable 48 hours post-infection 3
- Intranuclear inclusion bodies (Cowdry type A inclusions)
- Ground-glass appearance of nuclei
Cell Lines Used for HSV Culture
Common cell lines used for HSV culture include:
- Primary human fibroblasts
- MRC-5 cells
- Vero cells
- Baby hamster kidney cells
- Rabbit kidney cells 1
MRC-5 and rhabdomyosarcoma (RD) cells are equally sensitive for HSV detection, though early CPE may be easier to detect in MRC-5 cells 4.
Diagnostic Pitfalls
When examining viral cultures for HSV, be aware of these potential pitfalls:
- Only a minority of cases (28%) may show numerous cells with classic viral cytopathic changes 5
- Inflammation may obscure cytologic findings (severe in 22% of cases) 5
- Blood and degenerative changes can mask viral cytopathic effects 5
- Some HSV strains, particularly those from patients on acyclovir therapy, may not produce typical CPE even after 120 hours post-infection 6
Clinical Context
In this 20-year-old female patient, the clinical presentation strongly suggests primary genital herpes with meningeal involvement:
- Vesicular and ulcerative genital lesions
- Systemic symptoms (fever, chills, myalgias)
- Neurological symptoms (headache, photophobia, stiff neck)
- CSF showing mild pleocytosis with mononuclear cell predominance
- Rapid response to antiviral therapy
Typing of HSV Using Cell Culture
Typing of HSV using cell culture can be performed directly on infected cell cultures using:
- Fluorescein isothiocyanate (FITC)-labeled type-specific monoclonal antibodies
- Immunoperoxidase-labeled type-specific monoclonal antibodies
- Testing the cell supernatant by nucleic acid amplification tests (NAATs) with specifically designed primers 1
While PCR is now considered the gold standard for HSV detection with superior sensitivity, viral culture remains valuable as it demonstrates active infection and allows for antiviral sensitivity testing 1.