Failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man

MacLennan, Calman A.; Dunn, Glynis; Huissoon, Aarnoud; Kumararatne, Dinakantha; Martı́n, Javier; O’Leary, Paula; Thompson, R. A.; Osman, Husam; Wood, Philip; Minor, Philip D.; Wood, David; Pillay, Deenan

doi:10.1016/s0140-6736(04)16150-3

Cited by 141 publications

(102 citation statements)

References 30 publications

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“…1] associated with unusual disease presentations. Prolonged poliovirus excretion is a potentially important problem in polio eradication and although most immunodeficient individuals do not show prolonged excretion [42] one other individual with CVID and prolonged polio excretion but without C77G has been reported [43]. However, CVID is a very heterogeneous disease and although there is no overall increase in the frequency of C77G [44], it may be that C77G is associated with a subtype of disease or an unusual clinical course.…”

Section: Discussionmentioning

confidence: 99%

Unusual case presentations associated with the CD45 C77G polymorphism

Tchilian

Gil

Navarro

et al. 2006

Clinical and Experimental Immunology

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SummaryCD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases.

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Section: Discussionmentioning

confidence: 99%

Unusual case presentations associated with the CD45 C77G polymorphism

Tchilian

Gil

Navarro

et al. 2006

Clinical and Experimental Immunology

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“…PV mutants resistant to anti-PV inhibitors or anti-PV antibodies could emerge rapidly, because a mutant exists in a population of virus (10 3 to 10 5 ), if a single mutation was sufficient for resistance (Blondel et al, 1986;Crotty et al, 2001;de la Torre et al, 1992;Diamond et al, 1985;Pincus et al, 1986Pincus et al, , 1987. Actually, PV isolates from an immunodeficient case chronically infected with PV showed resistance to pleconaril, which is an anti-PV drug that targets the viral capsid proteins to prevent uncoating (Abdel-Rahman & Kearns, 1998), despite the absence of pleconaril treatment (MacLennan et al, 2004). In contrast, emergence of virus mutant resistant to inhibitors against cellular factors was limited, depending in part on the capacity of viral protein activities in the target step.…”

Section: Introductionmentioning

confidence: 99%

Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity

Arita

Wakita

Shimizu

2008

Journal of General Virology

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Poliovirus (PV) and enterovirus 71 (EV71) cause severe neurological symptoms in their infections of the central nervous system. To identify compounds with anti-PV and anti-EV71 activities that would not allow the emergence of resistant mutants, we performed drug screening by utilizing a pharmacologically active compound library targeting cellular factors with PV and EV71 pseudoviruses that encapsidated luciferase-encoding replicons. We have found that metrifudil (N-[2-methylphenyl]methyl)-adenosine) (an A2 adenosine receptor agonist), N 6 -benzyladenosine (an A1 adenosine receptor agonist) and NF449 (4,49,40,409-[carbonylbis[imino-5,1,3-benzenetriyl bis(carbonyl-imino)]] tetrakis (benzene-1,3-disulfonic acid) octasodium salt) (a Gs-a inhibitor) have anti-EV71 activity, and that GW5074 (3-(3, 5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)) (a Raf-1 inhibitor) has both anti-PV and anti-EV71 activities. EV71 mutants resistant to metrifudil, N 6 -benzyladenosine and NF449 were isolated after passages in the presence of these compounds, but mutants resistant to GW5074 were not isolated for both PV and EV71. The inhibitory effect of GW5074 was not observed in Sendai virus infection and the treatment did not induce the expression of OAS1 and STAT1 mRNA. Small interfering RNA treatment against putative cellular targets of GW5074, including Raf-1, B-Raf, Pim-1, -2, and -3, HIPK2, GAK, MST2 and ATF-3, did not consistently suppress PV replication. Moreover, downregulation of Raf-1 and B-Raf did not affect the sensitivity of RD cells to the inhibitory effect of GW5074. These results suggest that GW5074 has strong and selective inhibitory effect against the replication of PV and EV71 by inhibiting conserved targets in the infection independently of the interferon response.

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“…Antiviral agents do not confer immunity but could be used prophylactically as well as therapeutically. They could protect inactivated polio vaccine (IPV) recipients from PV infection, limit spread until immunity can be ensured and help clear vaccine-derived PV from persistently infected persons (7). The ideal drug would be safe, inexpensive, easy to use, stable, and manifest broad activity toward PV strains.…”

mentioning

confidence: 99%