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Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin

  1. Author:
    Alexandre, K. B.
    Gray, E. S.
    Lambson, B. E.
    Moore, P. L.
    Choge, I. A.
    Mlisana, K.
    Karim, S. S. A.
    McMahon, J.
    O'Keefe, B.
    Chikwamba, R.
    Morris, L.
  2. Author Address

    [Alexandre, Kabamba B.; Gray, Elin S.; Lambson, Bronwen E.; Moore, Penny L.; Choge, Isaac A.; Morris, Lynn] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa. [Mlisana, Koleka; Karim, Salim S. Abdool] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa, Durban, South Africa. [McMahon, James; O'Keefe, Barry] NCI, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21701 USA. [Chikwamba, Rachel] Ctr Sci & Ind Res, Pretoria, South Africa.;Morris, L, Natl Inst Communicable Dis, Private Bag X4, ZA-2131 Johannesburg, South Africa.;lynnm@nicd.ac.za
    1. Year: 2010
    2. Date: Jun
  1. Journal: Virology
    1. 402
    2. 1
    3. Pages: 187-196
  2. Type of Article: Article
  3. ISSN: 0042-6822
  1. 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 IC50 values were 0.4, 1.8 and 20.1 nM 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. (C) 2010 Elsevier Inc. All rights reserved.

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External Sources

  1. DOI: 10.1016/j.virol.2010.03.021
  2. WOS: 000277967500019

Library Notes

  1. Fiscal Year: FY2009-2010
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