Genetic Recombination in RNA Viruses

  • M. M. C. Lai
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 176)


Recombination in RNA viruses involves the exchange of genetic information between two nonsegmented RNA genomes, as distinct from the reassortment of RNA seen in viruses containing segmented genomes. The mechanism of RNA recombination appears to be similar to the generation of defective interfering (DI) RNA, since they both involve polymerase jumping during RNA synthesis. However, unlike the production of DI RNA, which is a relatively common phenomenon among RNA viruses, RNA recombination has so far only been demonstrated in a few RNA viruses. Homologous RNA recombination, which is defined as the exchange of two comparable RNA regions at precise locations, was first detected in poliovirus by Hirst (1962) and Ledinko (1963) in the early 1960s. Soon after, another member of the pircornavirus family, foot-and-mouth disease virus (FMDV), an aphthovirus, also was shown to undergo recombination (Pringle 1965). Subsequently, a series of temperature-sensitive (ts) mutants was used to determine recombination frequencies and do obtain a linear genetic recombination map (Cooper 1968, 1977). The definitive evidence for the occurrence of RNA recombination eventually came from the biochemical analysis of protein and RNA structure of the recombinant viruses (King et al. 1982). The second virus family to be shown to undergo RNA recombination is coronavirus (Lai et al. 1985). And more recently, several plant viruses, including brome mosaic virus and cowpea chlorotic mottle virus, also have been shown to undergo RNA recombination in rare situations (Bujarski and Kaesberg 1986; Allison et al. 1990). Thus, RNA recombination is being recognized increasingly as a general biological phenomenon among RNA viruses and probably plays an important role in viral biology and virus evolution. This chapter will deal mainly with homologous RNA recombination and will not discuss DI RNA, which is one form of nonhomologous RNA recombination.


Infectious Bronchitis Virus Mouse Hepatitis Virus Brome Mosaic Virus Cowpea Chlorotic Mottle Virus Western Equine Encephalitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Allison RF, Janda M, Ahlquist P (1989) Sequence of cowpea chlorotic mottle virus RNAs 2 and 3 and evidence of a recombination event during bromovirus evolution. Virology 172: 321–330PubMedCrossRefGoogle Scholar
  2. Allison RF, Thompson C, Ahlquist P (1990) Regeneration of a functional RNA virus genome by recombination between deletion mutants and requirement for cowpea chlorotic mottle virus 3a and coat genes for systemic infection. Proc Natl Acad Sci USA 87: 1820–1824PubMedCrossRefGoogle Scholar
  3. Angenent GC, Posthumus E, Brederode FT, Bol JF (1990) Genome structure of tobacco rattle virus strain PLB: further evidence on the occurrence of RNA recombination among tobraviruses. Virology 171: 271–274CrossRefGoogle Scholar
  4. Banner LR, Keck JG, Lai MMC (1990) A clustering of RNA recombination sites adjacent to a hypervariable region of the peplomer gene of murine coronavirus. Virology 175: 548–555PubMedCrossRefGoogle Scholar
  5. Banner LR, LAI MMC (1991) Random nature of coronavirus RNA recombination in the absence of selection pressure. Virology 185: 441–445PubMedCrossRefGoogle Scholar
  6. Baric RS, Shieh C-K, Stohlman SA, Lai MMC (1987) Analysis of intracellular small RNAs of mouse hepatitis virus: evidence for discontinuous transcription. Virology 156: 342–354PubMedCrossRefGoogle Scholar
  7. Baric RS, Fu K, Schaad MC, Stohlman SA (1990) Establishing a genetic recombination map for murine coronavirus strain A59 complementation groups. Virology 177: 646–656PubMedCrossRefGoogle Scholar
  8. Bujarski JJ, Kaesberg P (1986) Genetic recombination between RNA components of a multipartite plant virus. Nature 321: 528–531PubMedCrossRefGoogle Scholar
  9. Cascone PJ, Carpenter CD, Li XH, Simon AE (1990) Recombination between satellite RNAs of turnip crinkle virus. EMBO J. 9: 1709–1715PubMedGoogle Scholar
  10. Cooper PD (1968) A genetic map of poliovirus temperature-sensitive mutants. Virology 35: 584–596PubMedCrossRefGoogle Scholar
  11. Cooper PD (1977) Genetics of picornaviruses. In: Fraenkel-Conrat H, Wagner RR (eds) Comprehensive virology, vol 9. Plenum, New York, pp 133–208Google Scholar
  12. Hahn CS, Lustin S, Strauss EG, Strauss JH (1988) Western equine encephalitis virus is a recombinant virus. Proc Natl Acad Sci USA 85: 5997–6001PubMedCrossRefGoogle Scholar
  13. Haseloff J, Goelet P, Zimmern D, Ahlquist P, Dasgupta R, Kaesberg P (1984) Striking similarities in amino acid sequence among nonstructural proteins encoded by RNA viruses that have dissimilar genomic organization. Proc Natl Acad Sci USA 81: 4358–4362PubMedCrossRefGoogle Scholar
  14. Hayes W (1968) In: The genetics of bacteria and their viruses, 2nd edn. Blackwell, OxfordGoogle Scholar
  15. Hirst GK (1962) Genetic recombination with Newcastle disease virus, polioviruses and influenza virus. Cold Spring Harbor Symp Quant Biol 27: 303–309PubMedGoogle Scholar
  16. Hu W-S, Temin HM (1990) Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. Proc Natl Acad Sci USA 87: 1556–1560PubMedCrossRefGoogle Scholar
  17. Javier RT, Sedarati F, Stevens JG (1986) Two avirulent herpes simplex viruses generate lethal recombinants in vivo. Science 234: 746–749PubMedCrossRefGoogle Scholar
  18. Kassavetis GA, Chamberlin MJ (1981) Pausing and termination of transcription within the early region of bacteriophage T7 DNA in vitro. J Biol Chem 256: 2777–2786PubMedGoogle Scholar
  19. Katz JB, Henderson LM, Erickson GA (1990) Recombination in vivo of pseudorabies vaccine strains to produce new virus strains. Vaccine 8: 286–288PubMedCrossRefGoogle Scholar
  20. Keck JG, Stohlman SA, Soe LH, Makino S, Lai MMC (1987) Multiple recombination sites at the 5’-end of murine coronavirus RNA. Virology 156: 331–341PubMedCrossRefGoogle Scholar
  21. Keck JG, Matsushima GK, Makino S, Fleming JO, Vannier DM, Stohlman SA, Lai MMC (1988a) In vivo RNA—RNA recombination of coronavirus in mouse brain. J Virol 62: 1810–1813PubMedGoogle Scholar
  22. Keck JG, Soe LH, Makino S, Stohlman SA, Lai MMC (1988b) RNA recombination of murine coronaviruses: recombination between fusion-positive MHV-A59 and fusion-negative MHV-2. J Virol 62: 1989–1998PubMedGoogle Scholar
  23. Kew OM, Nottay BK (1984) Evolution of the oral polio vaccine strains in humans occurs by both mutation and intramolecular recombination. In: Chanock RM, Lerner RA (eds) Modern approaches to vaccines: molecular and chemical basis of virus virulence and immunogenicity. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 357–362Google Scholar
  24. King AMQ (1988) Recombination in positive strand RNA viruses. In: Domingo E, Holland JJ, Ahlquist P (eds) RNA genetics, vol 2. CRC, Boca Raton, FL, pp 149–165Google Scholar
  25. King AMQ, McCahon D, Slade WR, Newman JWI (1982) Recombination in RNA. Cell 29: 921–928PubMedCrossRefGoogle Scholar
  26. King AMQ, McCahon D, Saunders K, Newman JWI, Slade WR (1985) Multiple sites of recombination within the RNA genome of foot-and-mouth disease virus. Virus Res 3: 373–384PubMedCrossRefGoogle Scholar
  27. Kirkegaard K, Baltimore D (1986) The mechanism of RNA recombination in poliovirus. Cell 47: 433–443PubMedCrossRefGoogle Scholar
  28. Kusters JG, Niesters HGM, Lenstra JA, Horzinek MC, van der Zeijst BAM (1989) Phylogeny of antigenic variants of avian coronavirus IBV. Virology 169: 217–221PubMedCrossRefGoogle Scholar
  29. Lai MMC (1990) Coronavirus: organization, replication and expression of genome. Annu Rev Microbiol 44: 303–333PubMedCrossRefGoogle Scholar
  30. Lai MMC, Baric RS, Makino S, Keck JG, Egbert J, Leibowitz JL, Stohlman SA (1985) Recombination between nonsegmented RNA genomes of murine coronaviruses. J Virol 56: 449–456PubMedGoogle Scholar
  31. Lake JR, Priston RAJ, Slade WR (1975) A genetic recombination map of foot-and-mouth disease virus. J Gen Virol 27: 355–367PubMedCrossRefGoogle Scholar
  32. Ledinko N (1963) Genetic recombination with poliovirus type 1: studies of crosses between a normal horse serum-resistant mutant and several guanidine-resistant mutants of the same strain. Virology 20: 107–119PubMedCrossRefGoogle Scholar
  33. Lee HJ, Shieh C-K, Gorbalenya AE, Koonin EV, La Monica N, Tuler J, Bagdzhadzhyan A, Lai MMC (1991) The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerases. Virology 180: 567–582PubMedCrossRefGoogle Scholar
  34. Luytjes W, Bredenbeek PJ, Noten AFH, Horzinek MC, Spaan WJM (1988) Sequence of mouse hepatitis virus A59 mRNA 2: indications for RNA-recombination between coronavirus and influenza C virus. Virology 166: 415–422PubMedCrossRefGoogle Scholar
  35. Makino S, Keck JG, Stohlman SA, Lai MMC (1986) High-frequency RNA recombination of murine coronaviruses. J Virol 57: 729–737PubMedGoogle Scholar
  36. Makino S, Fleming JO, Keck JG, Stohlman SA, Lai MMC (1987) RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers. Proc Natl Acad Sci USA 84: 6567–6571PubMedCrossRefGoogle Scholar
  37. McCahon D, King AMQ, Roe DS, Slade WR, Newman JWI, Cleary AM (1985) Isolation and biochemical characterization of intertypic recombinants of foot-and-mouth disease virus. Virus Res 3: 87–100PubMedCrossRefGoogle Scholar
  38. McCahon D, Slade WR, Priston RA, Lake JR (1971) An extended genetic recombination map of foot-and-mouth disease virus. J Gen Virol 35: 555–565CrossRefGoogle Scholar
  39. Meyers G, Tautz N, Dubovi EJ, Thiel H-J (1991) Viral cytopathogenicity correlated with integration of ubiquitin-coding sequences. Virology 180: 602–616PubMedCrossRefGoogle Scholar
  40. Mills DR, Dobkin C, Kramer FR (1978) Template-determined, variable rate of RNA chain elongation. Cell 15: 541–550PubMedCrossRefGoogle Scholar
  41. Minor PD, John A, Ferguson M, Icenogle JP (1986) Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccine. J Gen Virol 67: 693–706PubMedCrossRefGoogle Scholar
  42. Pringle CR (1965) Evidence of genetic recombination in foot-and-mouth disease virus. Virology 25: 48–54PubMedCrossRefGoogle Scholar
  43. Rao ALN, Hall TC (1990) Requirement for a viral trans-acting factor encoded by brome mosaic virus RNA-2 provides strong selection in vivo for functional recombinants. J Virol 64: 2437–2441PubMedGoogle Scholar
  44. Steinhauer DA, Holland JJ (1986) Direct method for quantitation of extreme polymerase error frequencies at selected single base sites in viral RNA. J Virol 57: 219–228PubMedGoogle Scholar
  45. Tolskaya EA, Romanova LI, Blinov VM, Victorova EG, Sinyakov AN, Kolesnikova MS, Agol VI (1987) Studies on the recombination between RNA genomes of poliovirus: the primary structure and nonrandom distribution of crossover regions in the genomes of intertypic poliovirus recombinants. Virology 161: 54–61PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1992

Authors and Affiliations

  • M. M. C. Lai
    • 1
  1. 1.Howard Hughes Medical Institute and Department of MicrobiologyUniversity of Southern California School of MedicineLos AngelesUSA

Personalised recommendations