title: Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin.
abstract: Griffithsin (GRFT), Cyanovirin-N (CV-N) and Scytovirin (SVN) are lectins that inhibit HIV-1 infection by binding to multiple mannose-rich glycans on the HIV-1 envelope glycoproteins (Env). Here we show that these lectins neutralize subtype C primary virus isolates in addition to Env-pseudotyped viruses obtained from plasma and cervical vaginal lavages. Among 15 subtype C pseudoviruses, the median IC(50) values were 0.4, 1.8 and 20.1nM for GRFT, CV-N and SVN, respectively, similar to what was found for subtype B and A. Analysis of Env sequences suggested that concomitant lack of glycans at positions 234 and 295 resulted in natural resistance to these compounds, which was confirmed by site-directed mutagenesis. Furthermore, the binding sites for these lectins overlapped that of the 2G12 monoclonal antibody epitope, which is generally absent on subtype C Env. This data support further research on these lectins as potential microbicides in the context of HIV-1 subtype C infection.
authors.affiliation: National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Kabamba B
authors.initials: KB
authors.lastname: Alexandre
authors.forename: Elin S
authors.initials: ES
authors.lastname: Gray
authors.forename: Bronwen E
authors.initials: BE
authors.lastname: Lambson
authors.forename: Penny L
authors.initials: PL
authors.lastname: Moore
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Choge
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Salim S Abdool
authors.initials: SS
authors.lastname: Karim
authors.forename: James
authors.initials: J
authors.lastname: McMahon
authors.forename: Barry
authors.initials: B
authors.lastname: O'Keefe
authors.forename: Rachel
authors.initials: R
authors.lastname: Chikwamba
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
mesh_terms: D000328:Adult; D020418:Algal Proteins / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology*; D005260:Female; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D037102:Lectins / Q000494:pharmacology*; D008358:Mannose / Q000378:metabolism*; D008565:Membrane Proteins; D008826:Microbial Sensitivity Tests; D009500:Neutralization Tests; D037121:Plant Lectins; D010949:Plasma / Q000821:virology; D011485:Protein Binding; D014621:Vagina / Q000821:virology; D055815:Young Adult
chemical_list: D020418:Algal Proteins; D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D037102:Lectins; D008565:Membrane Proteins; D037121:Plant Lectins; C514793:gp120 protein, Human immunodeficiency virus 1; C474342:scytovirin protein, S varium; C107733:cyanovirin N; D008358:Mannose; C499654:griffithsin protein, Griffithsia
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