{ "id": "epbe5h161f", "slug": "virus-isolation", "title": "Virus isolation", "updated": "2026-10-15", "topic_path": [ { "id": "life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/topics/life" }, { "id": "life.microbes", "label": "Microorganisms and fungi", "api_url": "https://www.edgepedia.org/api/v1/topics/life.microbes" }, { "id": "life.microbes.viruses", "label": "Viruses and acellular agents", "api_url": "https://www.edgepedia.org/api/v1/topics/life.microbes.viruses" } ], "geo": [ { "id": "geo.nongeo.t1800.life", "label": "Non-geographic · 1800 to 1945: Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.life", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1800", "label": "Non-geographic · 1800 to 1945", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800" }, { "id": "geo.nongeo.t1800.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.life" } ] }, { "id": "geo.nongeo.t1946.life", "label": "Non-geographic · 1946 to 2000: Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1946", "label": "Non-geographic · 1946 to 2000", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946" }, { "id": "geo.nongeo.t1946.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1946.life" } ] } ], "excerpt": "Virus isolation is a laboratory method that grows a virus from a clinical sample in cell culture, eggs, or animals, long the gold standard for viral diagnosis.", "snippet": "Virus isolation is a laboratory method that grows a virus from a clinical sample in cell culture, eggs, or animals, long the gold standard for viral diagnosis.", "node": "life.microbes.viruses", "markdown": "# Virus isolation\n\nVirus isolation is a laboratory method that separates and propagates a virus from a clinical sample by inoculating a permissive host system, such as cell culture, embryonated eggs, or animals, to recover a viable, replicating isolate. For decades it was regarded as the gold standard for the laboratory diagnosis of viral disease, but it is slow and requires considerable technical expertise.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) It remains the approach of choice when a viable isolate is needed and, historically, when viable and nonviable virus had to be differentiated; for an infection not characteristic of any single virus, molecular panels and metagenomic sequencing are now generally used, with culture as a possible adjunct.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06)\n\n| Key fact | Detail |\n|---|---|\n| Product | A viable, propagating isolate, not merely a positive signal; useful when live virus, viable-versus-nonviable distinction, or open-ended identification is required[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) |\n| Time to cytopathic effect | Herpes simplex virus within 24 h; most viruses 5–10 days; cytomegalovirus averages 10–30 days[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) |\n| Rapid format | Shell-vial centrifugation at 700 × g for 1 h gives results for common viruses within 24–48 h[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) |\n| Sensitivity versus PCR | For human metapneumovirus, 67.7% sensitive and 99.4% specific versus real-time RT-PCR[2](https://link.springer.com/article/10.1186/1471-2334-10-170); for SARS-CoV-2, 58% of RT-PCR-positive samples were culture-positive[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9046102/) |\n| Viral-load dependence | SARS-CoV-2 isolation probability was 100% at Ct <22 and 3.1% at Ct >27[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9046102/) |\n| Containment | SARS-CoV-2 handling, including culture, is governed by a site- and activity-specific risk assessment; WHO permits, depending on the local risk assessment, less stringent risk control measures for virus isolation and propagation of currently circulating strains[4](https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-characterisation-update-standard-laboratory-protocols.pdf) |\n\n## How it works\n\nA mixed sample contains virus together with host debris, bacteria, and inhibitors. Inoculating a permissive host does two things at once: only virus able to enter and replicate in that host expands, and each replication cycle multiplies the virus far above its input level. In the 1949 report by [John F. Enders](https://www.edgepedia.org/john-f-enders), [Thomas H. Weller](https://www.edgepedia.org/thomas-h-weller), and [Frederick C. Robbins](https://www.edgepedia.org/frederick-c-robbins), human embryonic tissue cultures inoculated with poliovirus were maintained for 67 days, and over 52 days at least \\( 10^{16} \\)-fold more virus particles were recovered than had been initially inoculated.[5](https://doi.org/10.1126/science.109.2822.85) • [6](https://www.nature.com/articles/d42859-020-00014-7)\n\nWhether a host works depends on viral entry factors and the intracellular replication machinery. SARS-CoV-2, for example, grows in cells expressing ACE2 and TMPRSS2, while lines lacking suitable receptors do not support its growth.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC7543926/) The most common visible consequence of replication is the [cytopathic effect](https://www.edgepedia.org/cytopathic-effect) (CPE), defined as morphologic change in a monolayered culture resulting from viral infection; a syncytium is CPE arising from fusion of adjacent cells.[8](https://clsi.org/media/2436/m41ae_sample.pdf) CPE takes forms including loss of adherence, cell rounding, vacuoles, syncytia, inclusion bodies, and complete lysis.[9](https://bio.libretexts.org/Bookshelves/Microbiology/Introduction_to_Microbiology_%28Liu_et_al.%29/07%3A_Acellular_Pathogens/7.05%3A_Isolation_Culture_and_Identification_of_Viruses)\n\n## How it is done\n\nThe critical elements of a viral culture procedure are specimen collection, processing, and inoculation; cell culture selection, assessment, maintenance, and quality control; isolate detection and identification; and reporting and interpretation.[8](https://clsi.org/media/2436/m41ae_sample.pdf)\n\n**Collection and transport.** The best specimens are collected during the first 3 days after symptom onset, using Dacron or polyester swabs with plastic shafts; calcium alginate swabs must not be used.[10](https://www.dshs.texas.gov/laboratory-services/programs-laboratories/microbiology-unit/viral-isolation/viral-testing) Swabs go into 2–3 ml of viral transport medium containing antibiotics, a buffered salt solution, a protein such as albumin or gelatin, and a pH indicator.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) • [10](https://www.dshs.texas.gov/laboratory-services/programs-laboratories/microbiology-unit/viral-isolation/viral-testing) Samples travel on wet ice; labile viruses such as RSV, CMV, and VZV lose infectivity with delayed transport, and longer transit requires freezing at −70°C on dry ice.[10](https://www.dshs.texas.gov/laboratory-services/programs-laboratories/microbiology-unit/viral-isolation/viral-testing) Infectious titer declines rapidly at room temperature, so samples should be refrigerated immediately and cultured the same day or frozen at −80°C.[11](https://www.sciencedirect.com/science/article/pii/S0166093424000363)\n\n**Processing and inoculation.** Respiratory samples are vortexed, the swab discarded, the suspension centrifuged, and the supernatant used to inoculate cultures; heavily contaminated material such as stool may be passed through a 0.45-μm filter, which lowers the contamination rate but can trap pleomorphic filamentous viruses, so inoculating both filtered and unfiltered aliquots is recommended.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) • [11](https://www.sciencedirect.com/science/article/pii/S0166093424000363) • [12](https://www.intechopen.com/chapters/40221) Monolayers are seeded the day before infection, no more than two days in advance, and not passaged more than nine times.[13](https://www.atcc.org/resources/culture-guides/virology-culture-guide) An inoculum of 0.2–0.3 ml is added per tube, or adsorption inoculation applies inoculum directly to the decanted monolayer for 30–90 min at 35–37°C before fresh medium is added.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) Tube cultures are incubated at 35–37°C and examined microscopically daily for the first week and on alternate days thereafter.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06)\n\n**Detection, confirmation, and passage.** Hemadsorption, the adherence of red blood cells to monolayers mediated by viral hemagglutinin, identifies influenza, measles, mumps, and parainfluenza infections and can occur without CPE.[8](https://clsi.org/media/2436/m41ae_sample.pdf) • [13](https://www.atcc.org/resources/culture-guides/virology-culture-guide) In the shell-vial format the inoculated vial is spun at 700 × g for 1 h and viral antigen is stained before CPE with labeled monoclonal antibodies, giving results within 24–48 h.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) A culture without CPE should not be called negative; hemagglutination, hemadsorption, and electron microscopy serve as secondary evaluations.[12](https://www.intechopen.com/chapters/40221) Isolates are confirmed by immunostaining or PCR and quantified by TCID50 titration, calculated by the Reed–Muench or Spearman–Karber method, or by plaque assay reported as PFU/ml.[8](https://clsi.org/media/2436/m41ae_sample.pdf) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC7543926/) For stock production, supernatant is harvested when 50–75% of cells show CPE, clarified, aliquoted, and stored at −80°C.[4](https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-characterisation-update-standard-laboratory-protocols.pdf)\n\n## Origin\n\nIn 1908, [Karl Landsteiner](https://www.edgepedia.org/karl-landsteiner) and Irwin Popper injected spinal cord suspension from a polio patient into two [Old World](https://www.edgepedia.org/old-world) monkeys, which developed spinal cord lesions and, in the rhesus, paralysis of both legs.[6](https://www.nature.com/articles/d42859-020-00014-7) Albert B. Sabin and [Peter K. Olitsky](https://www.edgepedia.org/peter-k-olitsky) grew a monkey-adapted poliovirus strain in fragments of human embryonic brain, but concerns about central nervous tissue and vaccine safety motivated non-neural culture.[6](https://www.nature.com/articles/d42859-020-00014-7) The cell-culture substrate itself rested on the 1916 method of Peyton Rous and F. S. Jones for obtaining suspensions of living cells from fixed tissues.[14](https://doi.org/10.1084/jem.23.4.549) Vaccinia virus was grown in cell cultures as early as 1913, and in the 1930s smallpox and yellow fever viruses were propagated in cultures for vaccine production.[1](https://journals.asm.org/doi/10.1128/cmr.00002-06) • [15](https://www.ophrp.org/journal/view.php?number=415) George K. Hirst reported in 1941 that allantoic fluid from chick embryos infected with influenza virus agglutinates red cells, giving egg-grown influenza a quantitative readout.[16](https://doi.org/10.1126/science.94.2427.22)\n\nThe turning point came in 1949, when Enders, Weller, and Robbins reported cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues[5](https://doi.org/10.1126/science.109.2822.85); the methodological advance received the 1954 [Nobel Prize in Physiology or Medicine](https://www.edgepedia.org/nobel-prize-in-physiology-or-medicine) and enabled Salk to produce a successful polio vaccine.[6](https://www.nature.com/articles/d42859-020-00014-7) [Renato Dulbecco](https://www.edgepedia.org/renato-dulbecco)'s 1952 plaque assay, published in the [Proceedings of the National Academy of Sciences](https://www.edgepedia.org/proceedings-of-the-national-academy-of-sciences), made monolayer cultures countable by single virus particles.[17](https://doi.org/10.1073/pnas.38.8.747) In 1954, J. F. Enders and T. C. Peebles applied the poliovirus procedures to measles, obtaining eight cytopathogenic agents from blood or throat washings of patients, with cytopathic changes visible on day 7.[18](https://doi.org/10.3181/00379727-86-21073) • [19](https://ia601500.us.archive.org/19/items/EndersPeebles1954/Enders%20Peebles%201954.pdf) L. Hayflick and P. S. Moorhead's 1961 serial cultivation of human diploid cell strains, published in Experimental Cell Research, supplied a normal, finite-lifespan substrate.[20](https://doi.org/10.1016/0014-4827%2861%2990192-6) Diagnostic isolation expanded from the 1960s and accelerated around 1970 with commercially prepared cell lines and purified reagents.[15](https://www.ophrp.org/journal/view.php?number=415) • [1](https://journals.asm.org/doi/10.1128/cmr.00002-06)\n\n## Variants\n\n**Embryonated eggs and cell lines.** [Influenza](https://www.edgepedia.org/influenza) is propagated in embryonated chicken eggs 10–11 days old via allantoic, amniotic, chorioallantoic membrane, or yolk sac routes, with tissue-culture-propagated virus incubated at 33–35°C.[21](https://www.nature.com/articles/nprot.2014.180) Serial reproduction in eggs can alter hemagglutinin glycoproteins, producing egg-adapted viruses that differ from the original isolate.[22](https://www.mdpi.com/1422-0067/21/21/7978) MDCK cells are the standard mammalian host for influenza isolation; K. Tobita and colleagues reported plaque assay and primary isolation of influenza A in MDCK cells with trypsin in 1975[23](https://doi.org/10.1007/bf02123572), and Shuji Hatakeyama and colleagues reported in 2005 that MDCK cells engineered for enhanced α2,6-linked sialic acid expression improve isolation of human influenza viruses.[24](https://doi.org/10.1128/jcm.43.8.4139-4146.2005)\n\n**Engineered and mixed systems.** Primary cells have a finite lifespan and may harbor latent or adventitious viruses that overtake cultures or cause CPE identical to the target virus.[12](https://www.intechopen.com/chapters/40221) C. A. Gleaves and colleagues introduced low-speed centrifugation culture of CMV in MRC-5 shell vials in 1984[25](https://doi.org/10.1128/jcm.19.6.917-919.1984); later formats combined cell lines or engineered them for speed, including R-Mix shell vials for respiratory viruses (Caroline K. Y. Fong, Mi Kyung Lee, and Brigitte P. Griffith, 2000)[26](https://doi.org/10.1128/jcm.38.12.4660-4662.2000), the ELVIS genetically modified cell line for rapid HSV detection (Max R. Proffitt and Susan A. Schindler, 1995)[27](https://doi.org/10.1016/0928-0197%2895%2900011-v), and engineered BGMK cells for enteroviruses (Yung T. Huang and colleagues, 2002).[28](https://doi.org/10.1128/jcm.40.2.366-371.2002) No single line suffices: in one respiratory study, 3 of 16 samples showed CPE only in Mv1 Lu cells and 3 only in MDCK cells[22](https://www.mdpi.com/1422-0067/21/21/7978), and hMPV infects Vero E6 cells 5 to 20 times more efficiently than [LLC-MK2](https://www.edgepedia.org/llc-mk2) cells.[2](https://link.springer.com/article/10.1186/1471-2334-10-170)\n\n**Matching the host to the virus.** For SARS-CoV-2, routine culture runs in Vero CCL-81 or Vero E6 cells under Physical Containment Level 3; Calu-3 and Caco-2 support growth while A549, HeLa, and RD do not, and Calu-3 cells are preferred for variants of concern, for which Vero cells are less permissive.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC7543926/) • [4](https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-characterisation-update-standard-laboratory-protocols.pdf) Differentiated platforms extend the range further: well-differentiated human airway epithelium grown at an air–liquid interface supports [human bocavirus](https://www.edgepedia.org/human-bocavirus) and human coronavirus HKU1, which cannot be cultured on traditional cell lines.[29](https://onlinelibrary.wiley.com/doi/10.1111/irv.12297) Human intestinal enteroids made previously unculturable human norovirus propagable, with FUT2+ (secretor) enteroids permissive and bile acids such as GDCA acting as replication cofactors.[30](https://www.mdpi.com/1999-4915/18/2/238) [SARS-CoV-2](https://www.edgepedia.org/sars-cov-2) productively infects human gut enterocytes in enteroids[31](https://doi.org/10.1126/science.abc1669), and lung and colonic organoids have been used to identify SARS-CoV-2 inhibitors.[32](https://doi.org/10.1038/s41586-020-2901-9)\n\n## Applications\n\nIsolation produces material molecular methods cannot: progeny virus for animal inoculation to fulfill [Koch's postulates](https://www.edgepedia.org/kochs-postulates), which sequencing-only discovery cannot supply[29](https://onlinelibrary.wiley.com/doi/10.1111/irv.12297), and quantified infectious stocks for neutralization and antiviral testing. Culture also discovers new agents; human metapneumovirus was isolated in culture from young children with respiratory tract disease by Bernadette G. van den Hoogen and colleagues in 2001.[33](https://doi.org/10.1038/89098) An international culture of SARS-CoV-2 was reported in Melbourne, Australia.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC7543926/) Isolation also underpins adventitious-agent testing of biological products: in February 2025, highly pathogenic avian influenza A(H5N1) virus was detected in a fetal bovine serum lot during routine adventitious agent testing, using 9CFR-prescribed culture in Vero and primary fetal bovine kidney cells.[34](https://wwwnc.cdc.gov/eid/article/32/8/26-0077_article)\n\n## Limitations and alternatives\n\n**Turnaround and sensitivity.** HSV may produce visible CPE within 24 h, most viruses only after 5 to 10 days, and CMV averages 10 to 30 days[1](https://journals.asm.org/doi/10.1128/cmr.00002-06); some isolations take weeks to two months or more.[12](https://www.intechopen.com/chapters/40221) Among 100 consecutive RT-PCR-positive respiratory samples inoculated into Vero E6 cells, SARS-CoV-2 isolation succeeded in 58%; the median days from symptom onset was 2 for culture-positive and 15 for culture-negative samples, and isolation probability fell from 100% at Ct <22 to 3.1% at Ct >27.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9046102/) For hMPV, culture sensitivity was 67.7% and specificity 99.4% versus real-time RT-PCR, averaging 81.8% for specimens collected within 3 days of onset but 33.3% for days 4–7.[2](https://link.springer.com/article/10.1186/1471-2334-10-170) In a three-way comparison of 538 swabs, detection rates for seven respiratory viruses were 24.3% by culture, 20.8% by direct immunofluorescence assay, and 38.5% by multiplex PCR, with turnaround times of 3.7, 1.0, and 1.4 days.[35](https://synapse.koreamed.org/articles/1057136) Rapid antigen tests correlate better with viral culture than PCR does.[11](https://www.sciencedirect.com/science/article/pii/S0166093424000363) PCR-based methods detect viral genome rather than live infectious virus and can produce false positives.[22](https://www.mdpi.com/1422-0067/21/21/7978)\n\n**Failure modes.** Infectivity is fragile: 78% of viable SARS-CoV-2 virions were lost after four freeze–thaw cycles, freeze–thaw cannot be used for herpesviruses and other rapidly inactivated viruses, and the Omicron lineage was considerably more sensitive to freezing at −20°C and long-term storage than the ancestral strain, explaining lower culture success.[11](https://www.sciencedirect.com/science/article/pii/S0166093424000363) • [12](https://www.intechopen.com/chapters/40221) Other failure modes include the absence of a permissive cell line, bacterial or fungal contamination, and very low viral load; in the 2025 fetal bovine serum case, the USDA National Veterinary Services Laboratories could not confirm the isolation, and viral loads were estimated at probably less than 1 infectious particle per ml.[34](https://wwwnc.cdc.gov/eid/article/32/8/26-0077_article) Egg passage adapts viruses away from the original isolate, some viruses such as Lassa virus show very low PFU values that make CPE-based quantification not useful[22](https://www.mdpi.com/1422-0067/21/21/7978), and senescence of primary cells can be mistaken for virus-caused CPE.[12](https://www.intechopen.com/chapters/40221)\n\n**Biosafety.** Because it is often impossible to know what specimens might be infectious, all patient and laboratory specimens are handled under standard precautions.[8](https://clsi.org/media/2436/m41ae_sample.pdf) SARS-CoV-2 culture need not universally be performed under BSL-3: current guidance requires a site- and activity-specific risk assessment, and WHO permits, depending on the local risk assessment, less stringent risk control measures for virus isolation and propagation of currently circulating strains[4](https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-characterisation-update-standard-laboratory-protocols.pdf), high-consequence organoid work with H5N1 viruses has been performed under BSL-3+ containment[36](https://link.springer.com/article/10.1186/s12985-025-02714-w), and serum spiked with ≈7 \\( \\log_{10} \\) TCID50/ml was completely inactivated at 56°C for 30 minutes, supporting heat treatment of fetal bovine serum as a precaution.[34](https://wwwnc.cdc.gov/eid/article/32/8/26-0077_article)\n\n## References\n\n1. [Role of Cell Culture for Virus Detection in the Age of Technology (Leland & Ginocchio, Clin Microbiol Rev 2007)](https://journals.asm.org/doi/10.1128/cmr.00002-06)\n2. [Comparison of virus isolation using the Vero E6 cell line with real-time RT-PCR assay for the detection of human metapneumovirus (BMC Infect Dis, 2010)](https://link.springer.com/article/10.1186/1471-2334-10-170)\n3. [Viral culture and immunofluorescence for the detection of SARS-CoV-2 infectivity in RT-PCR positive respiratory samples](https://pmc.ncbi.nlm.nih.gov/articles/PMC9046102/)\n4. [Update of standard laboratory protocols for SARS-CoV-2 characterisation (AURORAE consortium / ECDC)](https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-characterisation-update-standard-laboratory-protocols.pdf)\n5. [John F. Enders, Thomas H. Weller, Frederick C. Robbins (1949). Cultivation of the Lansing Strain of Poliomyelitis Virus in Cultures of Various Human Embryonic Tissues. Science.](https://doi.org/10.1126/science.109.2822.85)\n6. [Culturing poliovirus in cells (Nature Milestones, 2020)](https://www.nature.com/articles/d42859-020-00014-7)\n7. [Virus isolation of SARS-CoV-2 for diagnostic and research purposes (Stelzer-Braid et al., 2020)](https://pmc.ncbi.nlm.nih.gov/articles/PMC7543926/)\n8. [CLSI M41: Viral Culture; Approved Guideline (sample)](https://clsi.org/media/2436/m41ae_sample.pdf)\n9. [7.05: Isolation Culture and Identification of Viruses (bio.libretexts.org)](https://bio.libretexts.org/Bookshelves/Microbiology/Introduction_to_Microbiology_%28Liu_et_al.%29/07%3A_Acellular_Pathogens/7.05%3A_Isolation_Culture_and_Identification_of_Viruses)\n10. [Viral Testing (Texas DSHS Laboratory)](https://www.dshs.texas.gov/laboratory-services/programs-laboratories/microbiology-unit/viral-isolation/viral-testing)\n11. [Culturing of SARS-CoV-2 from patient samples: Protocol for optimal virus recovery and assessment of infectious viral load (J Virol Methods, 2024)](https://www.sciencedirect.com/science/article/pii/S0166093424000363)\n12. [The Art of Animal Cell Culture for Virus Isolation (IntechOpen book chapter)](https://www.intechopen.com/chapters/40221)\n13. [Virology Culture Guide (ATCC)](https://www.atcc.org/resources/culture-guides/virology-culture-guide)\n14. [Peyton Rous, F. S. Jones (1916). A METHOD FOR OBTAINING SUSPENSIONS OF LIVING CELLS FROM THE FIXED TISSUES, AND FOR THE PLATING OUT OF INDIVIDUAL CELLS. The Journal of Experimental Medicine.](https://doi.org/10.1084/jem.23.4.549)\n15. [Traditional and Modern Cell Culture in Virus Diagnosis (Osong Public Health Res Perspect)](https://www.ophrp.org/journal/view.php?number=415)\n16. [George K. Hirst (1941). The Agglutination of Red Cells by Allantoic Fluid of Chick Embryos Infected with Influenza Virus. Science.](https://doi.org/10.1126/science.94.2427.22)\n17. [Renato Dulbecco (1952). Production of Plaques in Monolayer Tissue Cultures by Single Particles of an Animal Virus. Proceedings of the National Academy of Sciences.](https://doi.org/10.1073/pnas.38.8.747)\n18. [J. F. Enders, T. C. Peebles (1954). Propagation in Tissue Cultures of Cytopathogenic Agents from Patients with Measles.. Experimental Biology and Medicine.](https://doi.org/10.3181/00379727-86-21073)\n19. [Propagation in Tissue Cultures of Cytopathogenic Agents from Patients with Measles (Enders & Peebles, 1954)](https://ia601500.us.archive.org/19/items/EndersPeebles1954/Enders%20Peebles%201954.pdf)\n20. [The serial cultivation of human diploid cell strains (Experimental Cell Research, 1961)](https://doi.org/10.1016/0014-4827%2861%2990192-6)\n21. [Influenza A virus isolation, culture and identification (Eisfeld, Neumann & Kawaoka, Nature Protocols, 2014)](https://www.nature.com/articles/nprot.2014.180)\n22. [Cell Cultures for Virology: Usability, Advantages, and Prospects (Int J Mol Sci)](https://www.mdpi.com/1422-0067/21/21/7978)\n23. [K. Tobita and colleagues (1975). Plaque assay and primary isolation of influenza a viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin. Medical Microbiology and Immunology.](https://doi.org/10.1007/bf02123572)\n24. [Shuji Hatakeyama and colleagues (2005). Enhanced Expression of an α2,6-Linked Sialic Acid on MDCK Cells Improves Isolation of Human Influenza Viruses and Evaluation of Their Sensitivity to a Neuraminidase Inhibitor. Journal of Clinical Microbiology.](https://doi.org/10.1128/jcm.43.8.4139-4146.2005)\n25. [C A Gleaves and colleagues (1984). Rapid detection of cytomegalovirus in MRC-5 cells inoculated with urine specimens by using low-speed centrifugation and monoclonal antibody to an early antigen. Journal of Clinical Microbiology.](https://doi.org/10.1128/jcm.19.6.917-919.1984)\n26. [Caroline K. Y. Fong, Mi Kyung Lee, Brigitte P. Griffith (2000). Evaluation of R-Mix FreshCells in Shell Vials for Detection of Respiratory Viruses. Journal of Clinical Microbiology.](https://doi.org/10.1128/jcm.38.12.4660-4662.2000)\n27. [Rapid detection of HSV with an enzyme-linked virus inducible system™ (ELVIS™) employing a genetically modified cell line (Clinical and Diagnostic Virology, 1995)](https://doi.org/10.1016/0928-0197%2895%2900011-v)\n28. [Yung T. Huang and colleagues (2002). Engineered BGMK Cells for Sensitive and Rapid Detection of Enteroviruses. Journal of Clinical Microbiology.](https://doi.org/10.1128/jcm.40.2.366-371.2002)\n29. [Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses](https://onlinelibrary.wiley.com/doi/10.1111/irv.12297)\n30. [Organoids Gone Viral: A Comprehensive Review on Human Organoid Models to Study Viral Pathogenesis (Viruses, 2026)](https://www.mdpi.com/1999-4915/18/2/238)\n31. 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[Long-term culture of chicken tracheal organoids for the purpose of avian influenza virus research (Virology Journal, 2025)](https://link.springer.com/article/10.1186/s12985-025-02714-w)\n\n---\n*Topic: Encyclopedia › Life and health › Microorganisms and fungi › Viruses and acellular agents*\n\n*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/virus-isolation", "markdown_url": "https://www.edgepedia.org/virus-isolation.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Virus isolation\", Edgepedia (EdgeChat), https://www.edgepedia.org/virus-isolation. Edgepedia Community License 1.0.", "credit_md": "\"[Virus isolation](https://www.edgepedia.org/virus-isolation)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/virus-isolation](https://www.edgepedia.org/virus-isolation). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Virus isolation\", Edgepedia (EdgeChat), https://www.edgepedia.org/virus-isolation. Edgepedia Community License 1.0.", "speakable": "Virus isolation is a laboratory method that grows a virus from a clinical sample in cell culture, eggs, or animals, long the gold standard for viral diagnosis." }