serial passage


Summary: Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in VIRULENCE studies and the development of vaccines.

Top Publications

  1. Leyssen P, De Clercq E, Neyts J. The anti-yellow fever virus activity of ribavirin is independent of error-prone replication. Mol Pharmacol. 2006;69:1461-7 pubmed
    ..These data thus allow us to conclude that the in vitro anti-yellow fever virus activity of ribavirin is independent of error-prone replication. ..
  2. Ciota A, Ngo K, Lovelace A, Payne A, Zhou Y, Shi P, et al. Role of the mutant spectrum in adaptation and replication of West Nile virus. J Gen Virol. 2007;88:865-74 pubmed
    ..These data provide evidence of the importance of quasispecies dynamics in the adaptation of a flavivirus to new and changing environments and hosts, with little evidence of significant genetic change. ..
  3. Xu L, Bao L, Lv Q, Deng W, Ma Y, Li F, et al. A single-amino-acid substitution in the HA protein changes the replication and pathogenicity of the 2009 pandemic A (H1N1) influenza viruses in vitro and in vivo. Virol J. 2010;7:325 pubmed publisher
  4. Ciota A, Lovelace A, Jia Y, Davis L, Young D, Kramer L. Characterization of mosquito-adapted West Nile virus. J Gen Virol. 2008;89:1633-42 pubmed publisher
  5. Gulati S, Smith D, Air G. Deletions of neuraminidase and resistance to oseltamivir may be a consequence of restricted receptor specificity in recent H3N2 influenza viruses. Virol J. 2009;6:22 pubmed publisher
    ..However, deletions are independently generated at each passage, suggesting that virus with a full length NA RNA segment initiates the first round of infection. ..
  6. Stauffer Thompson K, Rempala G, Yin J. Multiple-hit inhibition of infection by defective interfering particles. J Gen Virol. 2009;90:888-99 pubmed publisher
    ..Our combined experiments and models provide a means to understand better how DIPs quantitatively impact the growth of viruses and the spread of their infections...
  7. Vasilakis N, Deardorff E, Kenney J, Rossi S, Hanley K, Weaver S. Mosquitoes put the brake on arbovirus evolution: experimental evolution reveals slower mutation accumulation in mosquito than vertebrate cells. PLoS Pathog. 2009;5:e1000467 pubmed publisher
    ..Moreover, these findings suggest that patterns of genetic evolution may differ between viruses replicating in mammalian and mosquito cells. ..
  8. Liu S, Zhang X, Gong L, Yan B, Li C, Han Z, et al. Altered pathogenicity, immunogenicity, tissue tropism and 3'-7kb region sequence of an avian infectious bronchitis coronavirus strain after serial passage in embryos. Vaccine. 2009;27:4630-40 pubmed publisher
    ..we attenuated a Chinese LX4-type nephropathogenic infectious bronchitis virus (IBV) strain, CK/CH/LHLJ/04V, by serial passage in embryonated chicken eggs...
  9. Song M, Pascua P, Lee J, Baek Y, Lee O, Kim C, et al. The polymerase acidic protein gene of influenza a virus contributes to pathogenicity in a mouse model. J Virol. 2009;83:12325-35 pubmed publisher
    ..To our knowledge, this is the first study that the isoleucine residue at position 97 in PA plays a key role in enhanced virulence in mice and is implicated in the adaptation of avian influenza viruses to mammalian hosts. ..

More Information


  1. Coffey L, Vasilakis N, Brault A, Powers A, Tripet F, Weaver S. Arbovirus evolution in vivo is constrained by host alternation. Proc Natl Acad Sci U S A. 2008;105:6970-5 pubmed publisher
    ..These results suggest that arbovirus adaptation and evolution is limited by obligate host alternation and predict that arboviral emergence via host range changes may be less frequent than that of single host animal RNA viruses...
  2. Hmwe S, Aizaki H, Date T, Murakami K, Ishii K, Miyamura T, et al. Identification of hepatitis C virus genotype 2a replicon variants with reduced susceptibility to ribavirin. Antiviral Res. 2010;85:520-4 pubmed publisher
    ..However, potential mechanisms of RBV resistance during HCV replication remain poorly understood. Serial passage of cells harboring HCV genotype 2a replicon in the presence of RBV resulted in the reduced susceptibility of ..
  3. Rodríguez Calvo T, Ojosnegros S, Sanz Ramos M, García Arriaza J, Escarmis C, Domingo E, et al. New vaccine design based on defective genomes that combines features of attenuated and inactivated vaccines. PLoS ONE. 2010;5:e10414 pubmed publisher
    ..The design can be extended to any viral pathogen that encodes trans-acting gene products, allowing complementation between replication-competent, defective forms. ..
  4. Ling B, Veazey R, Marx P. Nonpathogenic CCR2-tropic SIVrcm after serial passage and its effect on SIVmac infection of Indian rhesus macaques. Virology. 2008;379:38-44 pubmed publisher
    ..These results suggest that SIVrcm is nonpathogenic and may be useful for examining effective immune responses in SIV infection. ..
  5. Wang W, Duo J, Liu J, Ma C, Zhang L, Wei Q, et al. A mouse muscle-adapted enterovirus 71 strain with increased virulence in mice. Microbes Infect. 2011;13:862-70 pubmed publisher
    ..Further analysis revealed many mutations in different regions of the genome of mouse muscle-adapted virus. Collectively, these data demonstrated the mouse muscle-adapted EV71 0805a with increased virulence in mice. ..
  6. Hamir A, Kunkle R, Richt J, Greenlee J, Miller J. Serial passage of sheep scrapie inoculum in Suffolk sheep. Vet Pathol. 2009;46:39-44 pubmed publisher
  7. Rath B, Olshen R, Halpern J, Merigan T. Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance. Viruses. 2012;4:1212-34 pubmed publisher
    ..Multidrug pressure experiments lend understanding to mechanisms of HIV resistance as they bear upon new treatment strategies. ..
  8. Cuervo P, Santos A, Alves C, Menezes G, Silva B, Britto C, et al. Cellular localization and expression of gp63 homologous metalloproteases in Leishmania (Viannia) braziliensis strains. Acta Trop. 2008;106:143-8 pubmed publisher
    ..V.) braziliensis isolates remain unaltered during prolonged in vitro culture, suggesting that the proteolytic activity pattern is a stable phenotypic characteristic of these parasites. ..
  9. Lindenbach B. Measuring HCV infectivity produced in cell culture and in vivo. Methods Mol Biol. 2009;510:329-36 pubmed publisher
    ..This chapter describes methods for measuring the infectivity of HCV produced in cell culture or recovered from animals experimentally infected with the cell culture-produced virus. ..
  10. Jerzak G, Brown I, Shi P, Kramer L, Ebel G. Genetic diversity and purifying selection in West Nile virus populations are maintained during host switching. Virology. 2008;374:256-60 pubmed publisher
    ..Thus, the abundant genetic variation contributed to WNV populations through infection of mosquitoes and the strong purifying selection contributed by infection of birds may be maintained despite frequent host switching. ..
  11. Sierra M, Airaksinen A, González López C, Agudo R, Arias A, Domingo E. Foot-and-mouth disease virus mutant with decreased sensitivity to ribavirin: implications for error catastrophe. J Virol. 2007;81:2012-24 pubmed
    ..Implications for lethal mutagenesis are discussed. ..
  12. Yuste E, Borderia A, Domingo E, Lopez Galindez C. Few mutations in the 5' leader region mediate fitness recovery of debilitated human immunodeficiency type 1 viruses. J Virol. 2005;79:5421-7 pubmed
  13. Scully L, Bidochka M. Serial passage of the opportunistic pathogen Aspergillus flavus through an insect host yields decreased saprobic capacity. Can J Microbiol. 2005;51:185-9 pubmed
    ..Propagation of the opportunist A. flavus through the insect host G. mellonella resulted in a diminished capacity to grow on an alternate substrate, while maintaining or increasing its ability to use the host as a nutrient supply. ..
  14. Shinya K, Hatta M, Yamada S, Takada A, Watanabe S, Halfmann P, et al. Characterization of a human H5N1 influenza A virus isolated in 2003. J Virol. 2005;79:9926-32 pubmed
    ..This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans. ..
  15. Lindenbach B, Evans M, Syder A, Wölk B, Tellinghuisen T, Liu C, et al. Complete replication of hepatitis C virus in cell culture. Science. 2005;309:623-6 pubmed
    ..HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals. ..
  16. Bungyoku Y, Shoji I, Makine T, Adachi T, Hayashida K, Nagano Fujii M, et al. Efficient production of infectious hepatitis C virus with adaptive mutations in cultured hepatoma cells. J Gen Virol. 2009;90:1681-91 pubmed publisher
    ..The J6/JFH1-derived mutant viruses presented here would be a good tool for producing HCV particles with enhanced infectivity and for studying the molecular mechanism of HCV entry. ..
  17. Bell J, St Charles J, Murphy A, Rathinam V, Plovanich Jones A, Stanley E, et al. Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice. BMC Microbiol. 2009;9:57 pubmed publisher
    ..In the experimental study, the five colonizing strains were passaged four times in mice. For three strains, serial passage produced increased incidence and degree of pathology and decreased time to develop pathology; disease shifted ..
  18. Hensley S, Das S, Bailey A, Schmidt L, Hickman H, Jayaraman A, et al. Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science. 2009;326:734-6 pubmed publisher
  19. Tsunekuni R, Ito H, Otsuki K, Kida H, Ito T. Genetic comparisons between lentogenic Newcastle disease virus isolated from waterfowl and velogenic variants. Virus Genes. 2010;40:252-5 pubmed publisher
    ..These results suggest that in addition to the F cleavage site sequence, these two amino acids in HN protein are also related to the pathogenicity of NDV in chickens...
  20. Yamada K, Park C, Noguchi K, Kojima D, Kubo T, Komiya N, et al. Serial passage of a street rabies virus in mouse neuroblastoma cells resulted in attenuation: potential role of the additional N-glycosylation of a viral glycoprotein in the reduced pathogenicity of street rabies virus. Virus Res. 2012;165:34-45 pubmed publisher
    ..Taken together, we propose that the number of N-glycosylation sites in the G protein is one of the determinants of the pathogenicity of street rabies viruses...
  21. Perales C, Beach N, Gallego I, Soria M, Quer J, Esteban J, et al. Response of hepatitis C virus to long-term passage in the presence of alpha interferon: multiple mutations and a common phenotype. J Virol. 2013;87:7593-607 pubmed publisher
    ..The results suggest that multiple, independent mutational pathways can confer IFN-? resistance to HCV and might explain why no unified picture has been obtained regarding IFN-? resistance in vivo...
  22. García Arriaza J, Domingo E, Escarmis C. A segmented form of foot-and-mouth disease virus interferes with standard virus: a link between interference and competitive fitness. Virology. 2005;335:155-64 pubmed
    b>Serial passage of foot-and-mouth disease virus (FMDV) in BHK-21 cells at high multiplicity of infection resulted in dominance of particles containing defective RNAs that were infectious by complementation in the absence of standard viral ..
  23. Puri S, Chandra R. Plasmodium vinckei: selection of a strain exhibiting stable resistance to arteether. Exp Parasitol. 2006;114:129-32 pubmed
    ..Cross-sensitivity studies have shown that apart form resistance to related derivatives like artemether and artesunic acid, the derived parasites also show resistance to quinine and mefloquine. ..
  24. Ferguson D, Wade Evans A, Elsley W, Sangster R, Silvera P, MacManus S, et al. Preparation and characterization of new challenge stocks of SIVmac32H J5 following rapid serial passage of virus in vivo. J Med Primatol. 2007;36:131-42 pubmed
    ..These stocks display more robust peripheral persistence and tissue pathology in cynomolgus macaques and should prove valuable analysing recombinant vaccines based upon SIVmacJ5 transgenes. ..
  25. Domenech P, Reed M. Rapid and spontaneous loss of phthiocerol dimycocerosate (PDIM) from Mycobacterium tuberculosis grown in vitro: implications for virulence studies. Microbiology. 2009;155:3532-43 pubmed publisher
    ..It is essential that researchers undertaking in vivo virulence studies confirm the presence of PDIM within all recombinant clones and the parental strains they are derived from. ..
  26. Maree F, Blignaut B, de Beer T, Visser N, Rieder E. Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses. Virus Res. 2010;153:82-91 pubmed publisher
    ..Therefore, recombinant SAT viruses engineered to express substitutions that induce GAG-binding could be exploited in the rational design of vaccine seed stocks with improved growth properties in cell cultures. ..
  27. McMeniman C, Lane A, Fong A, Voronin D, Iturbe Ormaetxe I, Yamada R, et al. Host adaptation of a Wolbachia strain after long-term serial passage in mosquito cell lines. Appl Environ Microbiol. 2008;74:6963-9 pubmed publisher
    ..After long-term serial passage in this cell line, we transferred the mosquito-adapted wMelPop into cell lines derived from two other mosquito ..
  28. Giri L, FEISS M, Bonning B, Murhammer D. Production of baculovirus defective interfering particles during serial passage is delayed by removing transposon target sites in fp25k. J Gen Virol. 2012;93:389-99 pubmed publisher
    ..Specifically, PFGE was used to detect defective genomes, determine defective genome sizes and quantify the amount of defective genome within a heterogeneous genome population of passaged virus...
  29. Orloff S, Kennedy M, Belperron A, Maddon P, McDougal J. Two mechanisms of soluble CD4 (sCD4)-mediated inhibition of human immunodeficiency virus type 1 (HIV-1) infectivity and their relation to primary HIV-1 isolates with reduced sensitivity to sCD4. J Virol. 1993;67:1461-71 pubmed
    ..Rather, an event that occurs after binding may account for the differences. This postbinding event or feature may be determined by regions of the envelope outside the CD4 binding site. ..
  30. Kimberlin R, Walker C, Fraser H. The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. J Gen Virol. 1989;70 ( Pt 8):2017-25 pubmed
    ..These findings are important in the search for the putative nucleic acid genome of the scrapie agent. ..
  31. Eckels K, Dubois D, Putnak R, Vaughn D, Innis B, Henchal E, et al. Modification of dengue virus strains by passage in primary dog kidney cells: preparation of candidate vaccines and immunization of monkeys. Am J Trop Med Hyg. 2003;69:12-6 pubmed
    ..A DENV-3 strain lost all monkey infectivity after PDK cell passage. Twelve vaccine candidates were selected for Phase 1 human trials through this selection process. ..
  32. Pugachev K, Guirakhoo F, Ocran S, Mitchell F, Parsons M, Penal C, et al. High fidelity of yellow fever virus RNA polymerase. J Virol. 2004;78:1032-8 pubmed
  33. Sanchez G, Bosch A, Gomez Mariano G, Domingo E, Pinto R. Evidence for quasispecies distributions in the human hepatitis A virus genome. Virology. 2003;315:34-42 pubmed
    ..The results indicate that despite antigenic conservation, HAV replicates as a complex distribution of mutants, a feature of viral quasispecies...
  34. Guirakhoo F, Weltzin R, Chambers T, Zhang Z, Soike K, Ratterree M, et al. Recombinant chimeric yellow fever-dengue type 2 virus is immunogenic and protective in nonhuman primates. J Virol. 2000;74:5477-85 pubmed
    ..The high replication efficiency, attenuation phenotype in mice and monkeys, immunogenicity and protective efficacy, and genomic stability of ChimeriVax-D2 justify it as a novel vaccine candidate to be evaluated in humans. ..
  35. Fujii Y, Goto H, Watanabe T, Yoshida T, Kawaoka Y. Selective incorporation of influenza virus RNA segments into virions. Proc Natl Acad Sci U S A. 2003;100:2002-7 pubmed
    ..The neuraminidase vRNA incorporation signal and others yet to be identified should provide attractive targets for the attenuation of influenza viruses in vaccine production and the design of new antiviral drugs. ..
  36. Tami C, Taboga O, Berinstein A, Núñez J, Palma E, Domingo E, et al. Evidence of the coevolution of antigenicity and host cell tropism of foot-and-mouth disease virus in vivo. J Virol. 2003;77:1219-26 pubmed
    ..These results suggest that the selective pressure exerted by host humoral immune response can play a role in both the selection and stability of antigenic FMDV variants and that such variants can manifest alterations in cell tropism. ..
  37. Race R, Meade White K, Raines A, Raymond G, Caughey B, Chesebro B. Subclinical scrapie infection in a resistant species: persistence, replication, and adaptation of infectivity during four passages. J Infect Dis. 2002;186 Suppl 2:S166-70 pubmed
    ..In some cases infectivity similar to the original 263K hamster scrapie strain was found after 2 or 3 serial mouse passages totaling 1200-1550 days. ..
  38. Hughes G, Mioulet V, Haydon D, Kitching R, Donaldson A, Woolhouse M. Serial passage of foot-and-mouth disease virus in sheep reveals declining levels of viraemia over time. J Gen Virol. 2002;83:1907-14 pubmed
    ..Here, the results are reported of a novel experiment designed specifically to assess the effects of serial passage of foot-and-mouth disease virus (FMDV) in experimental groups of sheep...
  39. Somerville G, Beres S, Fitzgerald J, Deleo F, Cole R, Hoff J, et al. In vitro serial passage of Staphylococcus aureus: changes in physiology, virulence factor production, and agr nucleotide sequence. J Bacteriol. 2002;184:1430-7 pubmed
    ..Aconitase specific activity decreased 38% (P < 0.001) by the sixth week in culture. During serial passage, S...
  40. Kanesa thasan N, Edelman R, Tacket C, Wasserman S, Vaughn D, Coster T, et al. Phase 1 studies of Walter Reed Army Institute of Research candidate attenuated dengue vaccines: selection of safe and immunogenic monovalent vaccines. Am J Trop Med Hyg. 2003;69:17-23 pubmed
    ..the results of initial safety testing of 10 live-attenuated dengue virus (DENV) vaccine candidates modified by serial passage in primary dog kidney (PDK) cells at the Walter Reed Army Institute of Research...
  41. Puri B, Nelson W, Henchal E, Hoke C, Eckels K, Dubois D, et al. Molecular analysis of dengue virus attenuation after serial passage in primary dog kidney cells. J Gen Virol. 1997;78 ( Pt 9):2287-91 pubmed publisher
    ..parent strain dengue-1 virus West Pac 74 and virulent strain 45AZ5 PDK-O, which was derived from the parent by serial passage in diploid foetal rhesus lung (FRhL-2) and mutagenized with 5-azacytidine...
  42. Ebert D. Experimental evolution of parasites. Science. 1998;282:1432-5 pubmed
    b>Serial passage experiments are a form of experimental evolution that is frequently used in applied sciences; for example, in vaccine development...
  43. Grazia Revello M, Baldanti F, Percivalle E, Sarasini A, De Giuli L, Genini E, et al. In vitro selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells. J Gen Virol. 2001;82:1429-38 pubmed
    ..These findings link EC and PMNL tropism and suggest that PMNL tropism is a late HCMV function. ..
  44. Pal R, Taylor B, Foulke J, Woodward R, Merges M, Praschunus R, et al. Characterization of a simian human immunodeficiency virus encoding the envelope gene from the CCR5-tropic HIV-1 Ba-L. J Acquir Immune Defic Syndr. 2003;33:300-7 pubmed
    ..After serial passage through 4 pigtails by blood and bone marrow transfer, virus from pigtail PBMCs had higher in vitro infectious ..
  45. Chen W, Wu H, Chiou S. E/NS1 modifications of dengue 2 virus after serial passages in mammalian and/or mosquito cells. Intervirology. 2003;46:289-95 pubmed publisher
    ..Some populations of the virus are subsequently selected by and genetically (at least in the E/NS1 portion of the viral genome) maintained in C6/36 (mosquito) cells during replicative competition...
  46. Halstead S, Marchette N. Biologic properties of dengue viruses following serial passage in primary dog kidney cells: studies at the University of Hawaii. Am J Trop Med Hyg. 2003;69:5-11 pubmed
    b>Serial passage at low dilution of seven different wild-type dengue (DEN) viruses into primary dog kidney (PDK) cell cultures placed selective pressure that resulted in the following changes from parental phenotype: smaller plaques in LLC-..
  47. Carson S, Chapman N, Hafenstein S, Tracy S. Variations of coxsackievirus B3 capsid primary structure, ligands, and stability are selected for in a coxsackievirus and adenovirus receptor-limited environment. J Virol. 2011;85:3306-14 pubmed publisher
  48. Abdel Malek S, Badran Y. Pseudomonas aeruginosa PAO1 adapted to 2-phenoxyethanol shows cross-resistance to dissimilar biocides and increased susceptibility to antibiotics. Folia Microbiol (Praha). 2010;55:588-92 pubmed publisher
    ..Outer membranes of adapted strain showed altered protein profile when examined by SDS-PAGE. ..
  49. Plyusnina A, Plyusnin A. Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture. Virol J. 2005;2:12 pubmed
    ..The observed survival time seems to be sufficient for transmission of newly formed recombinant hantaviruses in nature. ..
  50. Awobode H, Paul A, Sengoku Graham H, Clem R, Mateus Pinilla N, McAllister M. Serial monoxenous transmission of Toxoplasma gondii in cats. J Parasitol. 2013;99:1122-4 pubmed publisher
    ..gondii that has efficient direct transmission. The isolate of T. gondii that was able to be passaged in this manner has been designated the Dubey strain and cultured tachyzoites have been donated to a repository. ..
  51. Lahiri S, Alm R. Potential of Staphylococcus aureus isolates carrying different PBP2a alleles to develop resistance to ceftaroline. J Antimicrob Chemother. 2016;71:34-40 pubmed publisher
    ..These studies demonstrate that there is a low risk of generating ceftaroline-resistant MRSA isolates, which appears independent of any pre-existing variation in the PBP2a protein sequence or initial ceftaroline MIC. ..
  52. Wang X, Lin Y, Li Q, Liu Q, Zhao W, Du C, et al. Genetic Evolution during the development of an attenuated EIAV vaccine. Retrovirology. 2016;13:9 pubmed publisher
  53. Hou Y, Lin C, Yokoyama M, Yount B, Marthaler D, Douglas A, et al. Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets. J Virol. 2017;91: pubmed publisher