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HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env Glycan-specific lectin devoid of T-cell mitogenic activity

dc.contributor.author al, E
dc.contributor.author Arntzen, CJ
dc.contributor.author Barnett, BW
dc.contributor.author Cao, H
dc.contributor.author Husk, AS
dc.contributor.author Matoba, N
dc.contributor.author Montefiori, David Charles
dc.contributor.author Omura, S
dc.contributor.author Pickel, MM
dc.contributor.author Takahashi, A
dc.contributor.author Tanno, K
dc.date.accessioned 2011-06-21T17:31:32Z
dc.date.issued 2010
dc.identifier.issn 1932-6203
dc.identifier.uri https://hdl.handle.net/10161/4548
dc.description.abstract The development of a topical microbicide blocking the sexual transmission of HIV-1 is urgently needed to control the global HIV/AIDS pandemic. The actinomycete-derived lectin actinohivin (AH) is highly specific to a cluster of high-mannose-type glycans uniquely found on the viral envelope (Env). Here, we evaluated AH's candidacy toward a microbicide in terms of in vitro anti-HIV-1 activity, potential side effects, and recombinant producibility. Two validated assay systems based on human peripheral blood mononuclear cell (hPBMC) infection with primary isolates and TZM-bl cell infection with Env-pseudotyped viruses were employed to characterize AH's anti-HIV-1 activity. In hPMBCs, AH exhibited nanomolar neutralizing activity against primary viruses with diverse cellular tropisms, but did not cause mitogenicity or cytotoxicity that are often associated with other anti-HIV lectins. In the TZM-bl-based assay, AH showed broad anti-HIV-1 activity against clinically-relevant, mucosally transmitting strains of clades B and C. By contrast, clade A viruses showed strong resistance to AH. Correlation analysis suggested that HIV-1′s AH susceptibility is significantly linked to the N-glycans at the Env C2 and V4 regions. For recombinant (r)AH expression, we evaluated a tobacco mosaic virus-based system in Nicotiana benthamiana plants as a means to facilitate molecular engineering and cost-effective mass production. Biochemical analysis and an Env-mediated syncytium formation assay demonstrated high-level expression of functional rAH within six days. Taken together, our study revealed AH's cross-clade anti-HIV-1 activity, apparent lack of side effects common to lectins, and robust producibility using plant biotechnology. These findings justify further efforts to develop rAH toward a candidate HIV-1 microbicide. © 2010 Matoba et al.
dc.language.iso en_US
dc.relation.ispartof PLoS ONE
dc.relation.isversionof 10.1371/journal.pone.0011143
dc.title HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env Glycan-specific lectin devoid of T-cell mitogenic activity
dc.title.alternative
dc.type Journal article
dc.description.version Version of Record
duke.date.pubdate 2010-6-15
duke.description.issue 6
duke.description.volume 5
dc.relation.journal Plos One
pubs.begin-page e11143
pubs.issue 6
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences Section for AIDS Research & Development
pubs.volume 5


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