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

Nobuyuki Matoba, Adam S. Husk, Brian W. Barnett, Michelle M. Pickel, Charles J. Arntzen, David C. Montefiori, Atsushi Takahashi, Kazunobu Tanno, Satoshi Omura, Huyen Cao, Jason P. Mooney, Carl V. Hanson, Haruo Tanaka

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere11143
JournalPLoS One
Volume5
Issue number6
DOIs
StatePublished - 2010

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T-cells
Human immunodeficiency virus 1
Viruses
Lectins
neutralization
lectins
Polysaccharides
HIV-1
polysaccharides
T-lymphocytes
T-Lymphocytes
Assays
Anti-Infective Agents
anti-infective agents
HIV
viruses
Local Anti-Infective Agents
Tobacco
assays
Biotechnology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Matoba, N., Husk, A. S., Barnett, B. W., Pickel, M. M., Arntzen, C. J., Montefiori, D. C., ... Tanaka, H. (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), [e11143]. https://doi.org/10.1371/journal.pone.0011143

HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env Glycan-specific lectin devoid of T-cell mitogenic activity. / Matoba, Nobuyuki; Husk, Adam S.; Barnett, Brian W.; Pickel, Michelle M.; Arntzen, Charles J.; Montefiori, David C.; Takahashi, Atsushi; Tanno, Kazunobu; Omura, Satoshi; Cao, Huyen; Mooney, Jason P.; Hanson, Carl V.; Tanaka, Haruo.

In: PLoS One, Vol. 5, No. 6, e11143, 2010.

Research output: Contribution to journalArticle

Matoba, N, Husk, AS, Barnett, BW, Pickel, MM, Arntzen, CJ, Montefiori, DC, Takahashi, A, Tanno, K, Omura, S, Cao, H, Mooney, JP, Hanson, CV & Tanaka, H 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, vol. 5, no. 6, e11143. https://doi.org/10.1371/journal.pone.0011143
Matoba, Nobuyuki ; Husk, Adam S. ; Barnett, Brian W. ; Pickel, Michelle M. ; Arntzen, Charles J. ; Montefiori, David C. ; Takahashi, Atsushi ; Tanno, Kazunobu ; Omura, Satoshi ; Cao, Huyen ; Mooney, Jason P. ; Hanson, Carl V. ; Tanaka, Haruo. / HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env Glycan-specific lectin devoid of T-cell mitogenic activity. In: PLoS One. 2010 ; Vol. 5, No. 6.
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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.",
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