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Combinations of Griffithsin with Other Carbohydrate-Binding Agents Demonstrate Superior Activity Against HIV Type 1, HIV Type 2, and Selected Carbohydrate-Binding Agent-Resistant HIV Type 1 Strains

dc.contributor.authorFérir, Geoffreyen_US
dc.contributor.authorHuskens, Danaen_US
dc.contributor.authorPalmer, Kenneth E.en_US
dc.contributor.authorBoudreaux, Daniel M.en_US
dc.contributor.authorSwanson, Michael D.en_US
dc.contributor.authorMarkovitz, David M.en_US
dc.contributor.authorBalzarini, Janen_US
dc.contributor.authorSchols, Dominiqueen_US
dc.date.accessioned2013-06-25T18:43:19Z
dc.date.available2013-06-25T18:43:19Z
dc.date.issued2012-11en_US
dc.identifier.citationFérir, Geoffrey; Huskens, Dana; Palmer, Kenneth E.; Boudreaux, Daniel M.; Swanson, Michael D.; Markovitz, David M.; Balzarini, Jan; Schols, Dominique (2012). "Combinations of Griffithsin with Other Carbohydrate-Binding Agents Demonstrate Superior Activity Against HIV Type 1, HIV Type 2, and Selected Carbohydrate-Binding Agent-Resistant HIV Type 1 Strains." AIDS Research and Human Retroviruses 28(11): 1513-1523. <http://hdl.handle.net/2027.42/98459>en_US
dc.identifier.issn0889-2229en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/98459
dc.description.abstractAbstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high genetic barrier to resistance. We wanted to evaluate whether two mannose-specific CBAs, recognizing multiple and often distinct glycan structures on the HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1 strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with combination indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in antiviral potency of griffithsin (GRFT) up to ?12-fold (against HIV-1), ?8-fold (against HIV-2), and ?6-fold (against CBA-resistant HIV-1) was observed. In contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains, but remarkable synergy with HHA and GNA was observed against 2G12 mAb- and MVN-resistant HIV-1 strains (CI, 0.64 and 0.49, respectively). Overall, combinations of GRFT and other CBAs showed synergistic activity against HIV-1, HIV-2, and even against certain CBA-resistant HIV-1 strains. The CBAs tested appear to have distinct binding patterns on the gp120 envelope and therefore do not necessarily compete with each other's glycan binding sites on gp120. As a result, there might be no steric hindrance between two different CBAs in their competition for glycan binding (except for the HHA/GNA combination). These data are encouraging for the use of paired CBA combinations in topical microbicide applications (e.g., creams, gels, or intravaginal rings) to prevent HIV transmission.en_US
dc.publisherMary Ann Liebert, Inc., publishersen_US
dc.titleCombinations of Griffithsin with Other Carbohydrate-Binding Agents Demonstrate Superior Activity Against HIV Type 1, HIV Type 2, and Selected Carbohydrate-Binding Agent-Resistant HIV Type 1 Strainsen_US
dc.typeArticleen_US
dc.subject.hlbsecondlevelMedicine (General)en_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.identifier.pmid22607556en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/98459/1/aid%2E2012%2E0026.pdf
dc.identifier.doi10.1089/aid.2012.0026en_US
dc.identifier.sourceAIDS Research and Human Retrovirusesen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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