HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env Glycan-specific lectin devoid of T-cell mitogenic activity
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.
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https://hdl.handle.net/10161/4548Published Version (Please cite this version)
10.1371/journal.pone.0011143Publication Info
Matoba, Nobuyuki; Husk, Adam S; Barnett, Brian W; Pickel, Michelle M; Arntzen, Charles
J; Montefiori, David C; ... Tanaka, Haruo (2010). HIV-1 neutralization profile and plant-based recombinant expression of actinohivin,
an Env Glycan-specific lectin devoid of T-cell mitogenic activity. PLoS ONE, 5(6). pp. e11143. 10.1371/journal.pone.0011143. Retrieved from https://hdl.handle.net/10161/4548.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine
Research & Development in the Department of Surgery, Division of Surgical Sciences
at Duke University Medical Center. His major research interests are viral immunology
and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing
antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory,
including mechanisms of neutralization and escape,

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