Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 1998 Oct;36(10):2893-9.
doi: 10.1128/JCM.36.10.2893-2899.1998.

Prolonged replication of a type 1 vaccine-derived poliovirus in an immunodeficient patient

O M Kew  1 , R W Sutter, B K Nottay, M J McDonough, D R Prevots, L Quick, M A Pallansch
Affiliations
Case Reports

Prolonged replication of a type 1 vaccine-derived poliovirus in an immunodeficient patient

O M Kew et al. J Clin Microbiol. 1998 Oct.

Abstract

VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by approximately 10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of approximately 3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started approximately 9.3 years earlier. This estimate is about the time (6. 9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
RNase T1 oligonucleotide fingerprints of the Sabin type 1 OPV reference strain (LSc 2ab) (left) and the day 158 isolate from the immunodeficient patient (right). Electrophoretic separation of oligonucleotides in the first dimension (separation by base composition) is from left to right and in the second dimension (separation by chain length) is from bottom to top. The longer oligonucleotides (chain lengths of ≥12 nucleotides) (18), which having unique sequences representing ∼15% of the genome, are resolved into patterns (fingerprints) that are highly characteristic of the RNA sequence.
FIG. 2
FIG. 2
VP1 nucleotide sequence alignment of the Sabin 1 reference strain (line 1), the day 11 isolate m variant (line 2), and the day 11 isolate M variant (line 3). Sabin 1 nucleotide positions are numbered according to the system of Nomoto et al. (28); those of the day 11 isolates are numbered similarly for comparability. Boldface letters identify codons of amino acid residues that form NAg I (2750 to 2785), NAg II (3140 to 3157), and NAg III (3338 to 3355) (25).
FIG. 3
FIG. 3
VP1 amino acid sequence alignment of the Sabin 1 reference strain (line 1), the day 11 isolate m variant (line 2), and the day 11 isolate M variant (line 3). Capsid amino acid positions are indicated by a four-digit number: the first digit identifies the virion protein, and the next three digits specify the residue position (e.g., 1001 indicates residue 1 of VP1). Boldface letters identify virion surface residues that form NAg I (1101 to 1112), NAg II (1221 to 1226), and NAg III (1287 to 1292) (25).
FIG. 4
FIG. 4
Tree summarizing sequence relatedness across the interval of nucleotides 3296 to 3445 (VP1/2A region) among the Sabin 1 vaccine strain, 3 isolates from the immunodeficient patient, 5 type 1 vaccine-related isolates from other immunodeficient VAPP patients in the United States, and 25 type 1 wild-type polioviruses isolated in different regions of the world from cases occurring within 5 years of onset of paralysis in the immunodeficient patient. BRA, Brazil; CHN, China (FJ, Fujian; GX, Guangxi); DOR, Dominican Republic; ELS, El Salvador; GEO, Georgia; GRE, Greece; IND, India; INO, Indonesia; MEX, Mexico; MOG, Mongolia; MOR, Morocco; PER, Peru; SEN, Senegal; SOA, South Africa; TAI, Taiwan; TUN, Tunisia; TUR, Turkey; USA, United States; VEN, Venezuela; and ZIM, Zimbabwe (35).
FIG. 5
FIG. 5
Estimation of the duration of chronic type 1 poliovirus vaccine infection from the rate of evolution of VP1 nucleotide sequences. (A) Rate of fixation of third-codon-position substitutions into VP1 from day 11 (M variant) to day 200, estimated from evolutionary distance calculations. On the abscissa, time zero is the date of onset of paralysis. The ordinate shows evolutionary distances from the sequence of the day 11 M variant. (B) Evolution rate calculated in panel A extrapolated back (dashed line) to zero substitutions in the Sabin 1 VP1. On the abscissa, time zero is the patient’s date of birth. The ordinate shows evolutionary distances from the Sabin 1 sequence (value for day 11 M variant = 31.2 VP1 third-position substitutions/100 nucleotides [Nts]).
FIG. 6
FIG. 6
Time course of chronic type 1 poliovirus vaccine infection estimated from the VP1 evolution rate shown in Fig. 5. If the infection was initiated by the last OPV dose received by the immunodeficient patient, then the actual duration of infection to day 200 would be reduced by 24%, from 9.8 years to 7.4 years.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aaronson R P, Young J F, Palese P. Oligonucleotide mapping: evaluation of its sensitivity by computer simulation. Nucleic Acids Res. 1982;10:237–246. - PMC - PubMed
    1. Alexander, J. P., Jr., H. E. Gary, Jr., and M. A. Pallansch. 1997. Duration of poliovirus excretion and its implications for acute flaccid paralysis surveillance: a review of the literature. J. Infect. Dis. 175(Suppl. 1):S176–S182. - PubMed
    1. Blondel B, Crainic R, Fichot O, Dufraisse G, Candrea A, Diamond D, Girard M, Horaud F. Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site. J Virol. 1986;57:81–90. - PMC - PubMed
    1. Centers for Disease Control and Prevention. Poliomyelitis prevention in the United States: introduction of a sequential vaccination schedule of inactivated poliovirus vaccine followed by oral poliovirus vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP) Morbid Mortal Weekly Rep. 1997;46:1–25. - PubMed
    1. Centers for Disease Control and Prevention. Prolonged poliovirus excretion in an immunodeficient person with vaccine-associated paralytic poliomyelitis. Morbid Mortal Weekly Rep. 1997;46:641–643. - PubMed

Publication types

MeSH terms

LinkOut - more resources