Occluding the Mannose Moieties on Human Immunodeficiency Virus Type 1 gp120 with Griffithsin Improves the Antibody Responses to Both Proteins in Mice

Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10021, USA.
AIDS research and human retroviruses (Impact Factor: 2.33). 07/2011; 28(2):206-14. DOI: 10.1089/aid.2011.0101
Source: PubMed


To assess the influence of mannosylated glycans on the immunogenicity of human immunodeficiency virus type 1 (HIV-1) Env proteins, we immunized mice with monomeric gp120 in the presence and absence of the mannose-binding protein, griffithsin (GRFT). For comparison, other groups of mice received the nonglycosylated HIV-1 Gag protein, with and without GRFT. Coimmunization with GRFT increased the anti-gp120 IgG reactivity significantly, but had no effect on the anti-Gag response. We also investigated the IgG response to GRFT and found that gp120, but not Gag, enhanced its immunogenicity. For both proteins, IgG1 antibodies dominated the IgG response, with IgG2b as the next most prevalent subclass. We conclude that gp120-GRFT complexes are more immunogenic than the free proteins, for both components, and that occluding the mannose moieties on monomeric gp120 can improve the humoral immune response to this protein.

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    • "The Ab response against Env requires multiple booster vaccinations and wanes quickly with a half-life of 30–60 days [32], [33]. One explanation is that N-linked oligomannose glycans on Env actively suppress immune cell functioning [34]–[37]. Indeed, vaccination studies in mice showed that de-mannosylated gp120 was more immunogenic than unmodified gp120 [38]. Taken together, a variety of Env properties may reduce its immunogenicity. "
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    PLoS ONE 06/2013; 8(6):e67309. DOI:10.1371/journal.pone.0067309 · 3.23 Impact Factor
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    • "HIV-1 gp120 can bind to many immune-system molecules, including CD4, CCR5, CXCR4 and MCLRs, thereby potentially interfering with key components of the immune system [16]. Suppressive effects of gp120 on diverse functions of a number of immune cells, including plasmacytoid DCs and monocyte-derived DCs, have been observed in vitro [17]–[19], and gp120 can also suppress immune responses in vivo [20]–[22], [24]. Given that Env vaccines are often delivered in considerable amounts (several hundred µg) to local sites, it is possible that the receptor-binding properties of these proteins could impair their immunogenicity [16]. "
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    PLoS ONE 05/2013; 8(5):e63785. DOI:10.1371/journal.pone.0063785 · 3.23 Impact Factor
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    ABSTRACT: It is generally believed that during the sexual transmission of HIV-1, the glycan-specific DC-SIGN receptor binds the virus and mediates its transfer to CD4(+) cells. The lectins griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN) inhibit HIV-1 infection by binding to mannose-rich glycans on gp120. We measured the ability of these lectins to inhibit both the HIV-1 binding to DC-SIGN and the DC-SIGN-mediated HIV-1 infection of CD4(+) cells. While GRFT, CV-N and SVN were moderately inhibitory to DC-SIGN binding, they potently inhibited DC-SIGN-transfer of HIV-1. The introduction of the 234 glycosylation site abolished HIV-1 sensitivity to lectin inhibition of binding to DC-SIGN and virus transfer to susceptible cells. However, the addition of the 295 glycosylation site increased the inhibition of transfer. Our data suggest that GRFT, CV-N and SVN can block two important stages of the sexual transmission of HIV-1, DC-SIGN binding and transfer, supporting their further development as microbicides.
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