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.author | Férir, Geoffrey | en_US |
dc.contributor.author | Huskens, Dana | en_US |
dc.contributor.author | Palmer, Kenneth E. | en_US |
dc.contributor.author | Boudreaux, Daniel M. | en_US |
dc.contributor.author | Swanson, Michael D. | en_US |
dc.contributor.author | Markovitz, David M. | en_US |
dc.contributor.author | Balzarini, Jan | en_US |
dc.contributor.author | Schols, Dominique | en_US |
dc.date.accessioned | 2013-06-25T18:43:19Z | |
dc.date.available | 2013-06-25T18:43:19Z | |
dc.date.issued | 2012-11 | en_US |
dc.identifier.citation | Férir, 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.issn | 0889-2229 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/98459 | |
dc.description.abstract | Abstract 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.publisher | Mary Ann Liebert, Inc., publishers | en_US |
dc.title | 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 | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Medicine (General) | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 22607556 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/98459/1/aid%2E2012%2E0026.pdf | |
dc.identifier.doi | 10.1089/aid.2012.0026 | en_US |
dc.identifier.source | AIDS Research and Human Retroviruses | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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