title: Inhibition of rhinovirus replication in vitro and in vivo by acid-buffered saline.
abstract: Human rhinoviruses (HRVs) are quite sensitive to low pH. To determine whether this characteristic might be a therapeutic target, we evaluated the sensitivity of HRV to low-pH buffers in vitro and in vivo. Our findings confirm that low pH inhibited replication of most HRVs and reduced the replication of influenza virus. Preliminary experiments verified that the surface pH of the human nasopharynx could be transiently lowered to pH approximately 4.0 by topical administration of citrate/phosphate (CP) buffers, which was well tolerated. In a pilot experimental colds study, intranasal administration of CP buffer, compared with normal saline, reduced viral shedding by 1 log unit (10(3) vs. 10(4) 50% tissue culture infective dose/mL; P<.01), although respiratory symptoms were not significantly reduced. These findings demonstrate that low-pH buffers have antiviral activity in vivo and suggest that a larger clinical trial is warranted to determine whether this approach could reduce rates of viral transmission.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, University of Wisconsin, Madison, WI 53792, USA. gern@medicine.wisc.edu
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.forename: Anne G
authors.initials: AG
authors.lastname: Mosser
authors.forename: Cheri A
authors.initials: CA
authors.lastname: Swenson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rennie
authors.forename: R James
authors.initials: RJ
authors.lastname: England
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Shaffer
authors.forename: Haruko
authors.initials: H
authors.lastname: Mizoguchi
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000166:cytology; D002021:Buffers; D019343:Citric Acid / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000737:chemistry / Q000821:virology; D009666:Nose / Q000737:chemistry / Q000187:drug effects / Q000821:virology; D010710:Phosphates / Q000008:administration & dosage / Q000494:pharmacology; D010850:Picornaviridae Infections / Q000188:drug therapy* / Q000503:physiopathology; D010865:Pilot Projects; D020545:Respiratory Mucosa / Q000166:cytology; D012229:Rhinovirus / Q000187:drug effects* / Q000472:pathogenicity; D012965:Sodium Chloride / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D002021:Buffers; D010710:Phosphates; D019343:Citric Acid; D012965:Sodium Chloride