Hygromycin B resistance mediates elimination of Leishmania virus from persistently infected parasites.
A series of pX63-HYG derivatives encoding Leishmania RNA virus 1-4 (LRV1-4) sequences were electroporated into cells of Leishmania strain M4147, a virus-infected strain of L. guyanensis. After 6 weeks of drug selection (hygromycin B), transfected parasites lacked detectable quantities of viral genomic double-stranded RNA, viral capsid protein, and RNA-dependent RNA polymerase (RDRP) activity. Evidence of viral infection was not recovered upon removal of the drug. While viral RNA transcripts were produced from electroporated expression vectors, as determined by reverse transcription-PCR, viral antigens were not detected, suggesting that the antiviral effects of hygromycin B are mediated through translation inhibition. A short-term selection study suggests that the LRV1-4 elimination may not only be a function of hygromycin B as a protein synthesis inhibitor but also possibly related to the mechanism of hygromycin B resistance in Leishmania strains.
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Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245-0549, USA.
Scheffter
S M
SM
Patterson
J L
JL
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D004351:Drug Resistance; D005814:Genes, Viral; D006801:Humans; D006921:Hygromycin B / Q000494:pharmacology*; D007892:Leishmania braziliensis; D018334:Leishmania guyanensis / Q000187:drug effects / Q000254:growth & development / Q000821:virology*; D019199:Leishmaniavirus / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis; D017735:Virus Latency
D000871:Anthelmintics; D011500:Protein Synthesis Inhibitors; D012367:RNA, Viral; D014764:Viral Proteins; D006921:Hygromycin B; D012324:RNA-Dependent RNA Polymerase