Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both ganciclovir and cidofovir
| Autor: | Seiji Ihara, Y. Isashiki, Y. Minamishima, K. Harada, Y. Eizuru |
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| Rok vydání: | 1997 |
| Předmět: |
Ganciclovir
Human cytomegalovirus DNA polymerase viruses Mutant Organophosphonates Cytomegalovirus medicine.disease_cause Antiviral Agents chemistry.chemical_compound Cytosine Organophosphorus Compounds Virology medicine Humans Gene Mutation biology virus diseases Drug Resistance Microbial General Medicine Sequence Analysis DNA medicine.disease chemistry Cytomegalovirus Infections DNA Viral biology.protein Cidofovir medicine.drug |
| Zdroj: | Archives of virology. 142(2) |
| ISSN: | 0304-8608 |
| Popis: | Both ganciclovir-sensitive and -resistant human cytomegaloviruses (HCMV) were isolated from a patient with aplastic anemia complicated with CMV retinitis and encephalitis. Ganciclovir-resistant clinical isolate, 93-1R, also showed cross-resistance against (s)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir). Molecular analysis of plaque-cloned strains revealed that a single nucleotide substitution at 2 160 (C to T) resulted in amino acid substitution at codon 501 from leucine to phenylalanine in the DNA polymerase gene. This mutation at codon 501 was easily identified by means of Alu I digestion of the selected PCR product. The same mutation existed in the DNA fragment amplified from the patient’s brain, suggesting that cross-resistant mutant 93-1R caused encephalitis. Furthermore, ganciclovir-resistant 93-1R-3 replicated much faster and was released more efficiently into the culture medium than ganciclovir-sensitive 91-7S-1. |
| Databáze: | OpenAIRE |
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