HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity.
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). Her...
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Public Library of Science (PLoS)
2010-06-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011143&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nobuyuki Matoba |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8da529b66fe640bba203fa649dd60c17 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8da529b66fe640bba203fa649dd60c172025-08-20T02:31:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-06-0156e1114310.1371/journal.pone.0011143HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity.Nobuyuki MatobaAdam S HuskBrian W BarnettMichelle M PickelCharles J ArntzenDavid C MontefioriAtsushi TakahashiKazunobu TannoSatoshi OmuraHuyen CaoJason P MooneyCarl V HansonHaruo TanakaThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011143&type=printable |
| spellingShingle | 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 HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity. PLoS ONE |
| title | HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity. |
| title_full | HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity. |
| title_fullStr | HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity. |
| title_full_unstemmed | HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity. |
| title_short | HIV-1 neutralization profile and plant-based recombinant expression of actinohivin, an Env glycan-specific lectin devoid of T-cell mitogenic activity. |
| title_sort | hiv 1 neutralization profile and plant based recombinant expression of actinohivin an env glycan specific lectin devoid of t cell mitogenic activity |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011143&type=printable |
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