Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Specialty Sites
    • COVID-19
    • Practice Current
    • Practice Buzz
    • Without Borders
    • Equity, Diversity and Inclusion
    • Innovations in Care Delivery
  • Collections
    • Topics A-Z
    • Residents & Fellows
    • Infographics
    • Patient Pages
    • Null Hypothesis
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Specialty Sites
    • COVID-19
    • Practice Current
    • Practice Buzz
    • Without Borders
    • Equity, Diversity and Inclusion
    • Innovations in Care Delivery
  • Collections
    • Topics A-Z
    • Residents & Fellows
    • Infographics
    • Patient Pages
    • Null Hypothesis
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in
  • Log out

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
  • Log out
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Residents & Fellows

Share

December 01, 1995; 45 (12 Suppl 8) Updated Proceedings of the Second International Conference on the Varicella-Zoster Virus

Molecular basis for a geographic variation of varicella-zoster virus recognized by a peptide antibody

Paul R. Kinchington, Stephanie E. Turse
First published December 1, 1995, DOI: https://doi.org/10.1212/WNL.45.12_Suppl_8.S13
Paul R. Kinchington
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephanie E. Turse
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Molecular basis for a geographic variation of varicella-zoster virus recognized by a peptide antibody
Paul R. Kinchington, Stephanie E. Turse
Neurology Dec 1995, 45 (12 Suppl 8) S13-S14; DOI: 10.1212/WNL.45.12_Suppl_8.S13

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
9

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

A live attenuated varicella vaccine, derived from a Japanese isolate, is currently being widely used to modulate disease caused by varicella-zoster virus. Differentiation of the vaccine from wild-type isolates has been and will continue to be critical in the assessment of the vaccine in the United States. This has largely relied upon identification of characteristic DNA polymorphisms in the vaccine strain. In this report, we describe the identification of a new sequence polymorphism, located in the N-terminal coding sequence of open reading frame (ORF) 10. This variation results in the synthesis of an ORF 10 protein that is differentially recognized by antibodies to an ORF 10 synthetic peptide. The variation appears to be completely restricted to Japanese strains, including that used for the live attenuated varicella vaccine. As such, this polymorphism and the antibodies that differentially recognize it could prove highly useful in the assessment of the Japanese vaccine in the United States.

NEUROLOGY 1995;45(Suppl 8): S13-S14

In westernized societies, the majority of varicella cases occur during childhood and are naturally selflimiting, with few long-term effects on health. However, varicella can have serious consequences in the immunocompromised, pregnant women, and newborns. It is also frequently more severe and complicated in adults, a problem common in third-world countries where primary infection often occurs later in life. In an approach to reduce the morbidity and mortality associated with varicella, a live attenuated varicella vaccine (LAVV) was developed by Takahashi et al. [1] Derived by passage of a Japanese varicella isolate in semipermissive guinea pig embryo fibroblasts, it has proved to be quite successful at preventing varicella and is now undergoing extensive clinical trial assessment to determine its suitability for widespread vaccination programs. Although LAVV induces protection from disease, it is not without problems. Evidence suggests that LAVV may not necessarily prevent wild-type varicella-zoster virus (VZV) infection, may even recombine with wild-type virus in vivo, and can itself go latent, reactivate, and cause zoster. [2,3]

The differentiation of LAVV from wild-type strains has been central in the epidemiologic and etiologic assessment of LAVV in clinical trials. This has largely been achieved by characterization of viral DNA fragments following restriction enzyme digestion and electrophoretic separation. Several VZV DNA fragments resulting from digestion with the enzymes Hpa I, BamHI, and Bgl I show mobilities characteristic of LAVV, either because of variations in the copy numbers of short, direct-repeat elements located in five regions of the VZV genome, [4] or, more rarely, as a result of DNA polymorphisms which affect the presence or absence of restriction enzyme sites. [5]

We have found and characterized two polymorphisms located in VZV open reading frame (ORF) 10, one of which appears to be geographically restricted to Japanese VZV strains. It was originally identified by antibodies directed against a synthetic peptide of ORF 10. The antibodies, which have been previously described, [6] are directed against the peptide YMECNLGTEHPSTDT, corresponding to the published N-terminal 14-amino-acid sequence of ORF 10 in the Dumas strain of VZV. [4] The antibodies react with a VZV-specific 47-kd polypeptide which is also a virion structural protein. [6] Extension of these studies has revealed that the antibodies do not react specifically with 47-kd polypeptides in cells infected with the Japanese LAVV strain. Analysis of 10 strains derived from six different US sites and from 10 unrelated isolates obtained from Osaka, Japan, revealed that the lack of reactivity extended to all Japanese strains but not to any American strains examined. The antibodies also failed to react with virus particles purified from LAVV-infected cells; since there appeared to be no difference in the polypeptide profiles of American and Japanese virus particle polypeptides in the 47-kd size range, it was concluded that lack of reactivity with the antibodies was the result of amino-acid sequence variations and not due to lack of synthesis of the ORF 10 protein by Japanese strains. The Nterminal portion of ORF 10 was therefore sequenced from several representative Japanese and American VZV strains.

The Figure 1 summarizes the sequence information obtained. The sequences were derived from polymerase chain reaction (PCR)-amplified DNA of the Nterminal region of ORF 10, using the primers TAGTACCACGTGGTATTATGAAC (N10F; corresponding to 12,041 to 12,063) and AAGGCGGAGACGGAGCAGTTTTA (N10R; corresponding to the complement of 12,311 to 12,332). The 290-bp amplified fragment was cloned using a TA Cloning Kit (In Vitrogen Corp.) and sequenced using a PCR-based DNA Sequitherm Kit (US Biochemical, Inc.). The DNA sequencing showed that all Japanese strains analyzed possessed a single base-pair change (C to A) at position 12,188, which is different from the published DNA sequence of Dumas and all American strains examined. The change resulted in a proline (found in the Dumas sequence) to histidine substitution at the 10th amino acid of ORF 10, which presumably caused the lack of reactivity with the anti-10 peptide antibodies. Further sequencing also revealed changes at positions 12,283 and 12,284 (both T-to-C changes) found in the Japanese strains examined, which caused a change of phenylalanine (in the Dumas strain) to serine at the 42nd amino acid of ORF 10 and the creation of a novel BamHI site. Interestingly, BamHI is one of the restriction enzymes used to differentiate LAVV from wild-type strains. However, these changes did not appear to be as tightly restricted, since they were found in three strains of American origin.

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 1. Diagrammatic representation of DNA sequencing of the N-terminal part of open reading frame (ORF) 10 and the variations found within a 290-base-pair fragment. (a) The relative position and transcriptional direction of ORF 10 is shown with respect to the VZV genome. A line represents the unique sequences, and bars represent the internal and terminal repeat sequences. (b) An expansion of VZV ORF 10, showing the relative position of the oligonucleotides used for PCR amplification (N10F, N10R) and the coordinates of the variations detected. (c) Expansion of the sequence variations found in VZV strains, both at the DNA and amino-acid sequence level, with the virus strains listed below the respective variations contained within their genomes. Z equals zoster isolate; V equals varicella isolate; Am equals American origin; Jap equals Japanese origin; Eur equals European origin. Dumas is the sequenced strain of VZV. [4] All Japanese strains were obtained from M. Takahashi, Osaka, Japan, and have previously been shown to be unrelated. [7] American strains were obtained as follows: Hagar-a, Dyke-b equals Pittsburgh, PA, isolates; Blocker, LaRue, Chase equals gift of A. Arvin, Stanford, CA; 32 equals gift of C. Grose, Iowa City, IA; MSD equals gift of E. Dunkel, Harvard, MA; Scott equals Bethesda, MD, isolate; Ellen, Webster equals obtained from American Type Culture Collection.

These polymorphisms and their differentiation by anti-peptide antibodies should prove useful in epidemiologic assessment of the Japanese-derived LAVV in American-based clinical trials, as they could be used to recognize American wild-type virus infections or disease in LAVV vaccinees. We have recently examined 18 reisolated strains from LAVV vaccinees (kindly supplied by A.A. Gershon, Columbia University, New York, NY). Of these, two were found to express 47-kd polypeptides which react with the anti-ORF 10 peptide antibodies, and further examination revealed that these were both wild-type isolates from LAVV recipients. We are currently examining additional LAVV reisolates for these variations as well as wild-type markers to identify possible in vivo recombinants.

  • Copyright 1995 by Advanstar Communication Inc.

REFERENCES

  1. 1.↵
    Takahashi M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S. Live attenuated varicella vaccine used to prevent the spread of varicella in hospital. Lancet 1974;2:1288-1290.
    OpenUrlPubMed
  2. 2.↵
    Ha K, Baba K, Ikeda T, Nishida M, Yabuuchi H, Takahashi M. Application of live attenuated varicella vaccine to children with acute leukemia or other malignancies without suspension of anticancer therapy. Pediatrics 1980;65:346-350.
    OpenUrl
  3. 3.
    Hammerschlag MR, Gershon AA, Steinberg SP, Gelb LW. Herpes zoster in an adult recipient of live attenuated varicella vaccine. J Infect Dis 1989;160:535-537.
    OpenUrl
  4. 4.↵
    Davison AJ, Scott JE. The complete DNA sequence of varicella-zoster virus. J Gen Virol 1986;67:1759-1816.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    Hayakawa Y, Torigoe S, Shiraki K, Yamanishi K, Takahashi M. Biological and biophysical markers of a varicella vaccine strain (Oka strain): identification of clinical isolates from vaccine recipients. J Infect Dis 1984;149:956-963.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    Kinchington PR, Hougland JK, Arvin AM, Ruyechan WT, Hay J. The varicella zoster virus immediate-early protein IE62 is a major component of virus particles. J Virol 1992;66:359-366.
    OpenUrl
  7. 7.↵
    Kinchington PR, Ling P, Pensiero MN, Gershon AA, Hay J, Ruyechan WT. A possible role for varicella zoster virus glycoprotein gpV in pathogenicity. Adv Exp Med Biol 1990;278:83-91.
    OpenUrl
View Abstract

Disputes & Debates: Rapid online correspondence

No comments have been published for this article.
Comment

NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.

  • Stay timely. Submit only on articles published within the last 8 weeks.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • 200 words maximum.
  • 5 references maximum. Reference 1 must be the article on which you are commenting.
  • 5 authors maximum. Exception: replies can include all original authors of the article.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Disputes & Debates Submission Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • REFERENCES
  • Figures & Data
  • Info & Disclosures
Advertisement

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 96 (3)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2021 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise