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Characterization of a spontaneous drug-resistant mutant of monkey B virus (Macacine herpesvirus 1)

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Abstract

Monkey B virus (Macacine herpesvirus 1; BV) is an α-herpesvirus of macaques that causes serious infections in humans. A spontaneous mutant resistant to penciclovir (PCV) was isolated. Several genes were sequenced to identify mutations potentially responsible for PCV resistance. A single nucleotide deletion in the thymidine kinase (TK) gene was identified. To confirm its role in PCV resistance, several TK recombinants were constructed. A TK-deletion virus and a recombinant carrying the mutation were both resistant to PCV, while a revertant was PCV-sensitive. These results demonstrate that spontaneous drug-resistant mutants of BV do occur and that the BV TK is responsible for sensitivity to PCV.

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References

  1. Bae PK, Kim JH, Kim HS, Chung IK, Paik SG, Lee CK (2006) Intracellular uptake of thymidine and antiherpetic drugs for thymidine kinase-deficient mutants of herpes simplex virus type 1. Antiviral Res 70:93–104

    Article  PubMed  CAS  Google Scholar 

  2. Black DH, Saliki JT, Eberle R (2002) Development of a green fluorescent protein reporter cell line to reduce biohazards associated with detection of infectious Cercopithecine herpesvirus 1 (monkey B virus) in clinical specimens. Comp Med 52:534–542

    PubMed  CAS  Google Scholar 

  3. Boulter EA, Thornton B, Bauer DJ, Bye A (1980) Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir. Br Med J 280:681–683

    Article  PubMed  CAS  Google Scholar 

  4. Chibo D, Druce J, Sasadeusz J, Birch C (2004) Molecular analysis of clinical isolates of acyclovir resistant herpes simplex virus. Antiviral Res 61:83–91

    Article  PubMed  CAS  Google Scholar 

  5. Cohen JI, Davenport DS, Stewart JA, Deitchman S, Hilliard JK, Chapman LE (2002) Recommendations for prevention of and therapy for exposure to B virus (Cercopithecine herpesvirus 1). Clin Infect Dis 35:1191–1203

    Article  PubMed  Google Scholar 

  6. Elmore D, Eberle R (2008) Monkey B virus (Cercopithecine herpesvirus 1). Comp Med 58:11–21

    CAS  Google Scholar 

  7. Focher F, Lossani A, Verri A, Spadari S, Maioli A, Gambino JJ, Wright GE, Eberle R, Black DH, Medveczky P, Medveczky M, Shugar D (2007) Sensitivity of monkey B virus (Cercopithecine herpesvirus 1) to antiviral drugs: role of thymidine kinase in antiviral activities of substrate analogs and acyclonucleosides. Antimicrob Agents Chemother 51:2028–2034

    Article  PubMed  CAS  Google Scholar 

  8. Gilbert C, Bestman-Smith J, Boivin G (2002) Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms. Drug Resist Updat 5:88–114

    Article  PubMed  CAS  Google Scholar 

  9. Holmes GP, Chapman LE, Stewart JA, Straus SE, Hilliard JK, Davenport DS (1995) Guidelines for the prevention and treatment of B-virus infections in exposed persons. The B virus working group. Clin Infect Dis 20:421–439

    PubMed  CAS  Google Scholar 

  10. Huff JL, Barry PA (2003) B-virus (Cercopithecine herpesvirus 1) infection in humans and macaques: potential for zoonotic disease. Emerg Infect Dis 9:246–250

    PubMed  Google Scholar 

  11. Morfin F, Thouvenot D (2003) Herpes simplex virus resistance to antiviral drugs. J Clin Virol 26:29–37

    Article  PubMed  CAS  Google Scholar 

  12. Rogers KM, Deatheridge M, Breshears MA, Chapman S, Black D, Ritchey JW, Payton M, Eberle R (2009) Type I IFN response to Papiine herpesvirus 2 (Herpesvirus papio 2; HVP2) determines neuropathogenicity in mice. Virology 386:280–289

    Article  PubMed  CAS  Google Scholar 

  13. Sarisky RT, Quail MR, Clark PE, Nguyen TT, Halsey WS, Wittrock RJ, O’Leary Bartus J, Van Horn MM, Sathe GM, Van Horn S, Kelly MD, Bacon TH, Leary JJ (2001) Characterization of herpes simplex viruses selected in culture for resistance to penciclovir or acyclovir. J Virol 75:1761–1769

    Article  PubMed  CAS  Google Scholar 

  14. Sasadeusz JJ, Tufaro F, Safrin S, Schubert K, Hubinette MM, Cheung PK, Sacks SL (1997) Homopolymer mutational hot spots mediate herpes simplex virus resistance to acyclovir. J Virol 71:3872–3878

    PubMed  CAS  Google Scholar 

  15. Simon MA, Daniel MD, Lee-Parritz D, King NW, Ringler DJ (1993) Disseminated B virus infection in a cynomolgus monkey. Lab Anim Sci 43:545–550

    PubMed  CAS  Google Scholar 

  16. Suzutani T, Ishioka K, De Clercq E, Ishibashi K, Kaneko H, Kira T, Hashimoto K, Ogasawara M, Ohtani K, Wakamiya N, Saijo M (2003) Differential mutation patterns in thymidine kinase and DNA polymerase genes of herpes simplex virus type 1 clones passaged in the presence of acyclovir or penciclovir. Antimicrob Agents Chemother 47:1707–1713

    Article  PubMed  CAS  Google Scholar 

  17. Weigler BJ (1992) Biology of B virus in macaque and human hosts: a review. Clin Infect Dis 14:555–567

    PubMed  CAS  Google Scholar 

  18. Whitely RJ, Hilliard JK (2001) Cercopithecine herpesvirus (B virus). In: Knipe DM, Howley PM (eds) Fields virology. Lippincott, Philadelphia, pp 2835–2848

    Google Scholar 

  19. Zwartouw HT, Humphreys CR, Collins P (1989) Oral chemotherapy of fatal B virus (Herpesvirus simiae) infection. Antiviral Res 11:275–283

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by PHS grant P40 12317.

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Correspondence to R. Eberle.

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Black, D.H., Maxwell, L.K. & Eberle, R. Characterization of a spontaneous drug-resistant mutant of monkey B virus (Macacine herpesvirus 1). Arch Virol 154, 1495–1497 (2009). https://doi.org/10.1007/s00705-009-0452-3

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  • DOI: https://doi.org/10.1007/s00705-009-0452-3

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