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Journal of Clinical Microbiology, September 2000, p. 3156-3160, Vol. 38, No. 9
Division of Viral and Rickettsial Diseases,
National Center for Infectious Diseases, Centers for Disease Control
and Prevention, U.S. Department of Health and Human Services,
Atlanta, Georgia 30333
Received 18 February 2000/Returned for modification 31 March
2000/Accepted 12 June 2000
A new method was developed to identify and differentiate
varicella-zoster virus (VZV) wild-type strains from the attenuated varicella Oka vaccine strain. The PCR technique was used to amplify a
VZV open reading frame (ORF) 62 region. A single specific amplicon of
268 bp was obtained from 71 VZV clinical isolates and several laboratory strains. Subsequent digestion of the VZV ORF 62 amplicons with SmaI enabled accurate strain differentiation (three
SmaI sites were present in amplicons of vaccine strain VZV,
compared with two enzyme cleavage sites for all other VZV strains
tested). This method accurately differentiated the Oka vaccine strain
from wild-type VZV strains circulating in countries representing all six populated continents. Moreover, the assay more reliably
distinguished wild-type Japanese strains from the vaccine strain than
did previously described methods.
Varicella-zoster virus (VZV) is the
etiologic agent of varicella (chicken pox), which usually occurs in
children, and zoster (shingles), which results from the reactivation of
a latent VZV infection. While VZV infections are usually mild, they
sometimes result in severe disease, particularly in immunocompromised
patients (5, 6, 11, 22). A live attenuated varicella vaccine (Oka strain), which confers protection in a high percentage of recipients (2, 7, 11, 23, 29), was licensed and recommended for use in the United States in 1995 (27).
Breakthrough varicella infections after exposure to wild-type VZV have
occasionally been noted among vaccinees (3, 9, 24, 28, 29),
and Oka vaccine may cause zoster in as many as 6% of immunocompromised
vaccinees (9, 12). To monitor potential VZV vaccine-related
complications, a technique that discriminates vaccine strain from
wild-type VZV is required.
In the past, identification of VZV strains was based on laborious
restriction fragment length polymorphism (RFLP) analysis of
preparations of viral DNA (15, 25), a method that also required successful culturing of VZV from lesions. Newer PCR methods have eliminated the need to propagate virus for VZV detection (18,
19, 21, 30). In the United States and Australia, wild-type and
vaccine strains have been effectively distinguished on the basis of the
presence or absence of BglI or PstI sites in
amplicons from VZV open reading frames (ORFs) 54 and 38, respectively (18, 19), although this technique fails to distinguish some Japanese wild-type strains (16).
More extensive genotyping, such as amplification analysis of
polymorphic repeat regions R5 and R2, was required to distinguish Oka
vaccine VZV from Japanese strains (20, 26), a technique that
also fails to identify some strains in Japan and the United Kingdom
(13, 14, 26).
Argaw et al. identified a sequence variation in VZV ORF 62 between the
Oka vaccine strain and the Oka parental strain and used these data as
the basis for a PCR-RFLP test (1). In this study we examined
various clinical samples and confirmed the ability of this PCR-RFLP
assay to differentiate vaccine strain from isolates obtained from patients.
Viruses, DNA preparation, sequencing.
VZV isolates
(excluding those provided by authors of this report) were kindly
provided by John Zaia (City of Hope Hospital, Los Angeles, Calif.),
Barbara Watson (Philadelphia Department of Public Health), Ann Arvin
(Stanford University, Palo Alto, Calif.), Dominic Dwyer (Westmead
Hospital, Sydney, Australia), and John Stewart and Joseph J. Esposito
(Centers for Disease Control and Prevention, Atlanta, Ga.). Material
from 71 specimens was available for testing. Isolates from various
geographic locations, including Japan (25 specimens), the United States
(26 specimens), Australia (9 specimens), Chad (5 specimens), Congo (5 specimens), Chile (2 specimens), Czech Republic (1 specimen), and
France (1 specimen) were collected between 1976 and 1999. VZV DNA
samples obtained from cells infected with the Oka vaccine strain and
three laboratory VZV strains (Webster, vzv11, and ROD) were also
examined. Thirty-nine of the clinical specimens came through general
practitioners and infectious disease physicians. Fifty-six preparations
of the viruses were isolates, and the remaining 15 were primary virus typed directly from vesicular fluid air dried onto glass slides, cotton
swabs, or skin scab lesions. DNA was prepared from vesicular fluid,
varicella scabs, and lysates of VZV-infected cells using NucleoSpin
Tissue Kits (CLONTECH Laboratories Inc., Palo Alto, Calif.).
Sequencing.
The nucleotide sequences of selected amplicons
were sequenced with an ABI Prism dye terminator cycle sequencing kit
(Applied Biosystems, Foster City, Calif.) according to the
manufacturer's instructions to verify their identity as VZV sequence.
Sequences were compared with the VZV ORF 62 sequences of the VZV Dumas
strain (GenBank accession number X04370), which were used to design the
PCR primers. The Genetics Computer Group (Madison, Wis.) package, DNASIS 2.1 (Hitachi Software, San Bruno, Calif.), and the OLIGO 5 program (National Biosciences, Inc., Plymouth, Minn.) were used for
computer analysis of nucleotide sequences.
Evaluation of ORF 62 primers.
The experimental primer
sequences used for these studies are described in Table
1. Initial testing of the amplification
conditions for each primer set was performed using a standard protocol.
Template DNA was prepared from HLF cells infected with VZV strain
Webster or from uninfected cells (negative control). PCR assays were
completed in a volume of 100 µl of a solution that contained 500 ng
of template DNA; 50 mM KCl; 10 mM Tris hydrochloride, pH 8.3; 5 mM
MgCl2; a 200 µM concentration (each) of dATP, dCTP, dGTP,
and dTTP; a 250 µM concentration of each primer; and 2.5 U of
Taq DNA polymerase (PCR Core kit [Boehringer Mannheim
Biochemicals, Indianapolis, Ind.] or GeneAmp PCR reagent kit with
AmpliTaq or AmpliTaq Gold DNA polymerase [Perkin-Elmer Cetus, Norwalk,
Conn.]). Reaction mixtures were passed through 25 cycles of
denaturation at 94°C for 1 min, a 1-min annealing step at a gradient
of temperatures (55 to 72°C), and a polymerization at 72°C for 1 min, followed by final extension at 72°C for 5 min (Mastercycler
gradient; Eppendorf Scientific Inc., Westbury, Conn.). Reaction
mixtures for hot-start PCR using AmpliTaq Gold polymerase were
incubated for 15 min at 96°C before the start of cycling. To control
for contamination, each primer pair in PCR cocktails was run using the
above cycling protocol in the absence of DNA template, with an
annealing temperature of 60°C.
0095-1137/00/$04.00+0
Improved Identification and Differentiation of Varicella-Zoster
Virus (VZV) Wild-Type Strains and an Attenuated Varicella Vaccine
Strain Using a VZV Open Reading Frame 62-Based PCR
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
TABLE 1.
ORF 62 VZV PCR primers
PCR assays. Detection of VZV genome variations in ORFs 38 and 54 was performed using the method described by LaRussa et al. (18). Detection of VZV genome variations in ORF 62 was performed as follows. Reaction mixtures included a 0.1 µM concentration of each oligonucleotide of upper (PKVL_6U [VZV genome position 106036]) and lower (PKVL_1L [VZV genome position 106284]) primers, which are complementary to a variable region of VZV ORF 62, in 100 µl of reaction mixture containing PCR Gold buffer (50 mM KCl; 15 mM Tris-hydrochloride, pH 8.0); 2.5 mM MgCl2; a 200 µM concentration (each) of dATP, dCTP, dGTP, and dTTP; and 2.5 U of AmpliTaq Gold DNA polymerase (PE Biosystems, Foster City, Calif.; Roche Molecular Biochemicals, Indianapolis, Ind.). For amplification, 500 ng of total DNA, prepared from VZV-infected cells using Nucleospin tissue kits, was used as a template. For clinical samples, PCR assays used a 1/100 aliquot of the DNA purified from a single lesion (scab or swab). An initial PCR hot-start step of 96°C for 15 min was followed by 30 cycles of amplification (1 min at 94°C, 1 min at 72°C) and a final extension step at 72°C for 3 min (Mastercycler gradient, Eppendorf Scientific Inc.).
For detection, 10 µl of PCR product was loaded onto precasted 4-to-25% gradient polyacrylamide gels in Tris-borate-EDTA (TBE) buffer (Novex, San Diego, Calif.) and run at 150 V for 1 h. Gels were stained with ethidium bromide to visualize DNA (0.5 µg/ml in TBE buffer, 15 min). Restriction reactions were performed using 5 to 10 µl of the PCR product adjusted to recommended endonuclease buffer and 10 U of SmaI, BglI, or PstI (New England Biolabs, Inc., Beverly, Mass.). Endonuclease-cleaved DNA products were separated by gel electrophoresis as described above. The 50- and 100-bp DNA ladders (GIBCO BRL, Gaithersburg, Md.) were used as DNA size markers.| |
RESULTS |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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ORF 62 region primer design and evaluation. A substitution of C for T in position 106262 (correspondent reference Dumas strain genome position denoted [4]) of the Oka vaccine genome compared with Oka parent strain DNA was recently identified (1). This substitution established an additional SmaI site in the Oka vaccine DNA and provided the basis for developing a new RFLP-PCR test for differentiating the VZV vaccine strain from wild-type strains. Oligonucleotide primers were designed to amplify a region of the VZV genome that codes for the C-terminal portion of the putative ORF 62 protein, approximately 200 nucleotides upstream and downstream of the mutation in position 106262.
Based on our experience with PCR, the most effective amplicon molecular size should be limited to between 250 and 350 bp in length. Amplicons within that size range usually provide optimal sensitivity for an assay, particularly for DNA amplification from clinical samples that may contain limited quantities of template. As such, we designed several primer sets and assessed their performance on both clinical specimens and laboratory stocks of VZV (Table 1). The G+C content, melting temperature, and length of the primers were chosen and analyzed using Oligo 5 primer design software to ensure they met the essential criteria for optimal PCR primers. In addition to the primer pair described previously (PHKR1 and PHKR2 [Table 1]), eight additional primers were designed (three upstream and five downstream of the mutation); in all, eight 20-mers, one 18-mer, and one 26-mer were assessed; the G+C content of the primers was between 55 and 70%. All of the primers were also analyzed by using OLIGO 5 software for the formation of dimers either within or between pairs; no significant theoretical misprinting was identified on any template. Twenty-one primer combinations were tested altogether, representing each of the three upper primers with each of seven lower primers. Representative results from temperature gradient PCR (55 to 75°C) for four of these experimental primer sets are presented in Fig. 1. Most of the primer pairs amplified a significant number of nonspecific reaction products (e.g., Fig. 1A to C). This was true regardless of whether a high concentration of DNA template (as with laboratory strains and the VZV vaccine strain) isolated from tissue culture or a low concentration from clinical samples was used (data not shown). On this basis, eight of the experimental primers were excluded from further analysis. The primer combination of PKVL6U-PKVL1L provided the best yield of specific product (on the basis of gel band intensity), produced the least amount of nonspecific amplification product, and performed well over a broad range of annealing temperatures (Fig. 1D). The last attribute makes this primer pair more versatile and will permit considerable flexibility in the selection of annealing temperature for VZV-specific PCR if a protocol demands it. For example, we were able to modify the original protocol, eliminating a 55°C annealing step, since at 72°C primer annealing and polymerase enzyme reaction take place with this primer set. Furthermore, the reaction products resulting from PCR using the primer pair PKVL6U-PKVL1L during SmaI RFLP analysis could be easily differentiated by gel electrophoresis. The 268-bp amplicon generated with this primer pair was predicted to produce 153-, 79-, and 36-bp (Oka parent and wild-type strains) or 112-, 79-, 41-, and 36-bp (Oka vaccine strain) SmaI fragment sets. As shown in Fig. 2, SmaI fragments of Oka vaccine strain amplicon can be clearly differentiated from DNA patterns obtained after SmaI cleavage of wild-type amplicons.
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Sensitivity and specificity of the ORF 62 PCR method. The primer set PKVL6U-PKVL1L was tested on a panel of VZV-positive and VZV-negative specimens. All VZV-positive samples generated a single specific amplicon 268 bp in size (Fig. 2). The product specificity of the 10 selected amplicons obtained from the PCR was also confirmed by sequence analysis (data not shown). There was no detectable PCR product after nucleic acid extraction and PCR amplification from tissue culture material containing the following human herpesviruses (HHVs): Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 (HSV-1) and HSV-2, and human herpesvirus (HHV) 6a, 6b, and 8. In addition, 20 human clinical (swabs and scabs) specimens that were negative both by virological tests and by independent PCR assays for VZV DNA were tested to assess specificity (data not shown). No amplicons were detected in PCR assays using these specimens. On further examination of the primers, we observed no product after PCR amplification with DNA of herpesvirus genome samples as well as DNA isolated from human, monkey, rabbit, mouse, rat, and Escherichia coli (data not shown). These results indicate that the PKVL6U-PKVL1L assay primers are highly specific for VZV.
The lower limit of detection by this method was defined as the smallest amount of DNA in a sample that produced detectable amplicon product (ethidium bromide staining in agarose or polyacrylamide gels) following 30 cycles of PCR. Working from serial dilutions of a preparation of VZV DNA of known concentration, we determined that the ORF 62 primer pair PKVL6U-PKVL1L is able to detect approximately 100 pg of DNA in a specimen. We determined that these primers detected VZV DNA in every specimen from a panel of scab and vesicle fluid clinical samples (12 specimens), even when as little as 1/50 of the DNA preparation was used for the PCR.PCR analysis of collected VZV DNA specimens.
Seventy-one DNA
preparations from cases of chickenpox and zoster were typed by the
LaRussa et al. method (ORF 54-ORF 38) (18) and by the ORF 62 method described here. For the ORF 54-ORF 38 method, 222-bp and
350-bp amplicons were produced and digested with PstI and
BglI restriction enzymes, respectively (results shown in
Table 2). Three of four possible
genotypes were detected: 32 specimens were identified as wild-type
PstI+ BglI
(i.e.,
possessing and lacking a PstI and a BglI
restriction site, respectively, and 34 specimens were identified as
wild-type BglI+ PstI+.
Additionally, nine DNAs were typed as Oka vaccine strain
(BglI+ PstI), among
which only two specimens, our Oka vaccine virus control specimen and
one U.S. case isolate obtained from a child after vaccination, are
considered genuine Oka vaccine specimens. The other seven viruses
detected as Oka vaccine strain by this method were wild-type
viruses isolated from lesions of varicella and zoster patients in
Japan. The fourth possible genotype (BglI
PstI) was not identified in this study.
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DISCUSSION |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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Several PCR methods that can detect and differentiate Oka-vaccine strain from wild-type strains have been described previously (18, 20, 26). This approach has proven to be rapid and is particularly useful as a diagnostic tool for the confirmation of atypical cases of varicella and zoster. It is also useful for the detection of VZV in archival clinical specimens, from which viable VZV is unlikely to be isolated. The most widely used clinical PCR method for discriminating VZV Oka vaccine DNA from wild-type virus is based on PCR-RFLP analysis targeting BglI and PstI sites in amplicons from VZV ORFs 54 and 38, respectively (18). In these studies, we confirmed that most of the non-Japanese VZV wild-type strains can be distinguished from the Oka vaccine strain by using the PstI marker in ORF 38. However, as noted previously (13, 14, 26) the application of this method for Japanese strains and probably some other Asian regions has been limited due to the circulation of strains related to Oka that cannot be distinguished from the Oka strain by using the ORF 38 marker. In the present study, seven wild-type Japanese strains with Oka-like genotypes were found.
The development of PCR methods for VZV strain differentiation has been hampered by the fact that the VZV genome is highly conserved and due to our limited information about the primary DNA sequence of the Oka vaccine strain. Argaw et al. (1) identified a mutation in ORF 62 of the Oka vaccine strain that is absent in the parental isolate from which it was derived, and this site has proven valuable for diagnostic purposes. This mutation, which introduces a new SmaI restriction site into the Oka vaccine strain, formed the basis for the development of the diagnostic test described here.
An additional advantage to the ORF 62 method is that strain discrimination can be accomplished using a single DNA amplification produced from one primer pair and a single restriction enzyme digestion. Thus, the method also requires half the cost, labor, and time of the ORF 54-ORF 38 method. Amplification with the PKVL6U-PKVL1L primer pair results in a PCR product that unambiguously indicates the presence of VZV DNA in test specimens. Subsequent digestion of this 268-bp amplicon with SmaI provides reliable differentiation of VZV Oka vaccine strain and wild-type strains.
Most importantly, the results of this study indicate that the ORF 62-based PCR method distinguishes even closely related wild-type clinical isolates of VZV from the Oka vaccine strain. One valuable benefit of the ORF 62 RFLP assay is that several SmaI sites are present in the targeted amplicon, which helps to monitor restriction enzyme activity during the assay.
The original ORF 62 primers we selected to perform this assay quite effectively amplified VZV DNA from specimens, but they also tended to produce a number of nonspecific reaction products. This was also true of most of the ORF 62 experimental primer pairs we examined in this study. While some of the primers described here may prove useful for alternative diagnostic applications, such as automated DNA or RNA hybridization techniques, the PKVL6U-PKVL1L primer combination clearly outperformed all others tested for RFLP analysis. This primer set generated no detectable nonspecific PCR product in VZV-positive specimens across a broad range of annealing temperatures and produced no detectable PCR product from DNA samples from closely related viruses, including HSV1, HSV2, HHV6a, HHV6b, HHV8, CMV, and EBV. Furthermore, a search of GenBank and EMBL nucleotide sequence databases, querying with the primer sequences described here, identified significant matches only with VZV ORF 62 DNA sequences.
The ORF 62-based PCR method described here successfully verified the presence of VZV both in purified virus DNA from laboratory strains and in a large number of clinical specimens isolated from countries encompassing six continents. Admittedly, we have thus far examined only small numbers of clinical isolates from countries that may or may not reflect VZV strains that are circulating throughout the continent. Nonetheless, testing of additional clinical specimens should help to strengthen the validity of this approach, particularly in specimens from countries where Oka-like strains may still be circulating. Protocols using this approach for diagnosing suspected chickenpox and zoster in clinical samples should be coupled with PCR, using primers specific for beta-globin gene DNA or other cellular markers to confirm that amplification conditions are optimal, thus minimizing false-negative results (8).
The ORF 62-based PCR-RFLP protocol described here should be readily adaptable for use in a variety of laboratories, including hospital facilities with PCR and gel electrophoresis capabilities. The present study extends the usefulness of PCR techniques as a diagnostic method for the detection and differentiation of VZV DNA in clinical specimens.
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ACKNOWLEDGMENTS |
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We thank the following individuals for providing VZV specimens for this study: Ann Arvin, John Zaia, Barbara Watson, Dominic Dwyer, John Stewart, and Joseph J. Esposito. We also thank William C. Reeves, Philip E. Pellett, and Naoki Inoue for valuable intellectual discussions during the completion of this study. Finally, we thank John O'Connor for assistance in editing the manuscript.
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FOOTNOTES |
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* Corresponding author. Mailing address: Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333. Phone: (404) 639-4040 or (404) 639-0066. Fax: (404) 639-4056. E-mail: vnl0{at}cdc.gov.
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REFERENCES |
|---|
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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| 1. | Argaw, T., J. I. Cohen, M. Klutch, K. Lekstrom, T. Yoshikawa, Y. Asano, and P. R. Krause. 2000. Nucleotide sequences that distinguish Oka vaccine from parental Oka and other varicella-zoster virus isolates. J. Infect. Dis. 181:1153-1157[CrossRef][Medline]. |
| 2. | Arvin, A. M., and A. A. Gershon. 1996. Live attenuated varicella vaccine. Annu. Rev. Microbiol. 50:59-100[CrossRef][Medline]. |
| 3. |
Asano, Y.,
S. Suga,
T. Yoshikawa,
I. Kobayashi,
T. Yazaki,
M. Shibata,
K. Tsuzuki, and S. Ito.
1994.
Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine.
Pediatrics
94:524-526 |
| 4. |
Davison, A. J., and J. E. Scott.
1986.
The complete DNA sequence of varicella-zoster virus.
J. Gen. Virol.
67:1759-1816 |
| 5. | Devine, S. M., and J. R. Wingard. 1994. Viral infections in severely immunocompromised cancer patients. Support Care Cancer 2:355-368[CrossRef][Medline]. |
| 6. |
Gatnash, A. A., and C. K. Connolly.
1995.
Fatal chickenpox pneumonia in an asthmatic patient on oral steroids and methotrexate.
Thorax
50:422-423 |
| 7. | Gershon, A. A. 1995. Varicella-zoster virus: prospects for control. Adv. Pediatr. Infect. Dis. 10:93-124[Medline]. |
| 8. | Gershon, A. A., and B. Forghani. 1995. Varicella-zoster virus, p. 601-613. In E. H. Lennette, D. A. Lennette, and E. T. Lennette (ed.), Diagnostic procedures for viral, rickettsial, and chlamydial infections, 7th ed. Marcel Dekker, New York, N.Y. |
| 9. | Gershon, A. A., P. LaRussa, I. Hardy, S. Steinberg, and S. Silverstein. 1992. Varicella vaccine: the American experience. J. Infect. Dis. 166(Suppl. 1):S63-S68. |
| 10. |
Gershon, A. A.,
S. Steinberg,
L. Gelb,
G. Galasso,
W. Borkowsky,
P. LaRussa, and A. Ferrara.
1985.
A multicentre trial of live attenuated varicella vaccine in children with leukaemia in remission.
Postgrad. Med. J.
61(Suppl. 4):73-78 |
| 11. | Gershon, A. A., S. P. Steinberg, P. LaRussa, A. Ferrara, M. Hammerschlag, and L. Gelb. 1988. Immunization of healthy adults with live attenuated varicella vaccine. J. Infect. Dis. 158:132-137[Medline]. |
| 12. | Hardy, I. B., A. Gershon, S. Steinberg, and P. LaRussa. 1991. The incidence of zoster after immunization with live attenuated varicella vaccine: a study in children with leukemia. N. Engl. J. Med. 325:1545-1550[Abstract]. |
| 13. | Hawrami, K., and J. Breuer. 1997. Analysis of United Kingdom wild-type strains of varicella-zoster virus: differentiation from the Oka vaccine strain. J. Med. Virol. 53:60-62[CrossRef][Medline]. |
| 14. | Hawrami, K., L. J. Hart, F. Pereira, S. Argent, B. Bannister, B. Bovill, D. Carrington, M. Ogilvie, S. Rawstorne, Y. Tryhorn, and J. Breuer. 1997. Molecular epidemiology of varicella-zoster virus in East London, England, between 1971 and 1995. J. Clin. Microbiol. 35:2807-2809[Abstract]. |
| 15. |
Hayakawa, Y.,
T. Yamamoto,
K. Yamanishi, and M. Takahashi.
1986.
Analysis of varicella-zoster virus DNAs of clinical isolates by endonuclease HpaI.
J. Gen. Virol.
67:1817-1829 |
| 16. | Hondo, R., Y. Yogo, M. Yoshida, A. Fujima, and S. Itoh. 1989. Distribution of varicella-zoster virus strains carrying a Pst-site-less mutation in Japan and DNA change responsible for the mutation. Jpn. J. Exp. Med. 59:233-237[Medline]. |
| 17. | Kuter, B. J., R. E. Weibel, H. A. Guess, H. Matthews, D. H. Morton, B. J. Neff, P. J. Provost, B. A. Watson, S. E. Starr, and S. A. Plotkin. 1991. Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies. Vaccine 9:643-647[CrossRef][Medline]. |
| 18. |
LaRussa, P.,
O. Lungu,
I. Hardy,
A. Gershon,
S. P. Steinberg, and S. Silverstein.
1992.
Restriction fragment length polymorphism of polymerase chain reaction products from vaccine and wild-type varicella-zoster virus isolates.
J. Virol.
66:1016-1020 |
| 19. | LaRussa, P., S. Steinberg, A. Arvin, D. Dwyer, M. Burgess, M. Menegus, K. Rekrut, K. Yamanishi, and A. Gershon. 1998. Polymerase chain reaction and restriction fragment length polymorphism analysis of varicella-zoster virus isolates from the United States and other parts of the world. J. Infect. Dis. 178:S64-S66. |
| 20. | Mori, C., R. Takahara, T. Toriyama, T. Nagai, M. Takahashi, and K. Yamanishi. 1998. Identification of the Oka strain of the live attenuated varicella vaccine from other clinical isolates by molecular epidemiologic analysis. J. Infect. Dis. 178:35-38[Medline]. |
| 21. | Nahass, G. T., M. J. Mandel, S. Cook, W. Fan, and C. L. Leonardi. 1995. Detection of herpes simplex and varicella-zoster infection from cutaneous lesions in different clinical stages with the polymerase chain reaction. J. Am. Acad. Dermatol. 32:730-733[CrossRef][Medline]. |
| 22. | Parnham, A. P., J. P. Flexman, B. M. Saker, and G. N. Thatcher. 1995. Primary varicella in adult renal transplant recipients: a report of three cases plus a review of the literature. Clin. Transplant. 9:115-118[Medline]. |
| 23. |
Plotkin, S. A.
1996.
Varicella vaccine.
Pediatrics
97:251-253 |
| 24. | Shiraki, K., K. Horiuchi, Y. Asano, K. Yamanishi, and M. Takahashi. 1991. Differentiation of oka varicella vaccine strain from wild varicella-zoster virus strains isolated from vaccinees and household contact. J. Med. Virol. 33:128-132[Medline]. |
| 25. |
Straus, S. E.,
J. Hay,
H. Smith, and J. Owens.
1983.
Genome differences among varicella-zoster virus isolates.
J. Gen. Virol.
64:1031-1041 |
| 26. | Takada, M., T. Suzutani, I. Yoshida, M. Matoba, and M. Azuma. 1995. Identification of varicella-zoster virus strains by PCR analysis of three repeat elements and a PstI-site-less region. J. Clin. Microbiol. 33:658-660[Abstract]. |
| 27. |
Takahashi, M.
1986.
Clinical overview of varicella vaccine: development and early studies.
Pediatrics
78:736-741 |
| 28. | Takayama, N., M. Minamitani, and M. Takayama. 1997. High incidence of breakthrough varicella observed in healthy Japanese children immunized with live attenuated varicella vaccine (Oka strain). Acta Paediatr. Jpn. 39:663-668[Medline]. |
| 29. |
Watson, B. M.,
S. A. Piercy,
S. A. Plotkin, and S. E. Starr.
1993.
Modified chickenpox in children immunized with the Oka/Merck varicella vaccine.
Pediatrics
91:17-22 |
| 30. | Yoshida, M., T. Tamura, and M. Hiruma. 1999. Analysis of strain variation of R1 repeated structure in varicella-zoster virus DNA by polymerase chain reaction. J. Med. Virol. 58:76-78[CrossRef][Medline]. |
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0095-1137/00/$04.00+0
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[Abstract] [Full Text] -
Parker, S. P., Quinlivan, M., Taha, Y., Breuer, J.
(2006). Genotyping of Varicella-Zoster Virus and the Discrimination of Oka Vaccine Strains by TaqMan Real-Time PCR.. J. Clin. Microbiol.
44: 3911-3914
[Abstract] [Full Text] -
Peters, G. A., Tyler, S. D., Grose, C., Severini, A., Gray, M. J., Upton, C., Tipples, G. A.
(2006). A Full-Genome Phylogenetic Analysis of Varicella-Zoster Virus Reveals a Novel Origin of Replication-Based Genotyping Scheme and Evidence of Recombination between Major Circulating Clades. J. Virol.
80: 9850-9860
[Abstract] [Full Text] -
Haddad, M. B., Hill, M. B., Pavia, A. T., Green, C. E., Jumaan, A. O., De, A. K., Rolfs, R. T.
(2005). Vaccine Effectiveness During a Varicella Outbreak Among Schoolchildren: Utah, 2002-2003. Pediatrics
115: 1488-1493
[Abstract] [Full Text] -
Hambleton, S., Gershon, A. A.
(2005). Preventing Varicella-Zoster Disease. Clin. Microbiol. Rev.
18: 70-80
[Abstract] [Full Text] -
Sauerbrei, A., Rubtcova, E., Wutzler, P., Schmid, D. S., Loparev, V. N.
(2004). Genetic Profile of an Oka Varicella Vaccine Virus Variant Isolated from an Infant with Zoster. J. Clin. Microbiol.
42: 5604-5608
[Abstract] [Full Text] -
Loparev, V. N., Gonzalez, A., Deleon-Carnes, M., Tipples, G., Fickenscher, H., Torfason, E. G., Schmid, D. S.
(2004). Global Identification of Three Major Genotypes of Varicella-Zoster Virus: Longitudinal Clustering and Strategies for Genotyping. J. Virol.
78: 8349-8358
[Abstract] [Full Text] -
Grose, C., Tyler, S., Peters, G., Hiebert, J., Stephens, G. M., Ruyechan, W. T., Jackson, W., Storlie, J., Tipples, G. A.
(2004). Complete DNA Sequence Analyses of the First Two Varicella-Zoster Virus Glycoprotein E (D150N) Mutant Viruses Found in North America: Evolution of Genotypes with an Accelerated Cell Spread Phenotype. J. Virol.
78: 6799-6807
[Abstract] [Full Text] -
Campsall, P. A., Au, N. H. C., Prendiville, J. S., Speert, D. P., Tan, R., Thomas, E. E.
(2004). Detection and Genotyping of Varicella-Zoster Virus by TaqMan Allelic Discrimination Real-Time PCR. J. Clin. Microbiol.
42: 1409-1413
[Abstract] [Full Text] -
Galil, K., Lee, B., Strine, T., Carraher, C., Baughman, A. L., Eaton, M., Montero, J., Seward, J.
(2002). Outbreak of Varicella at a Day-Care Center despite Vaccination. NEJM
347: 1909-1915
[Abstract] [Full Text] -
Loparev, V. N., McCaustland, K., Holloway, B. P., Krause, P. R., Takayama, M., Schmid, D. S.
(2000). Rapid Genotyping of Varicella-Zoster Virus Vaccine and Wild-Type Strains with Fluorophore-Labeled Hybridization Probes. J. Clin. Microbiol.
38: 4315-4319
[Abstract] [Full Text]
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