The lectins griffithsin, cyanovirin-N and scytovirin inhibit HIV-1 binding to the DC-SIGN receptor and transfer to CD4+ cells

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.

Short Communication: Inhibition of DC-SIGN-Mediated HIV-1 Infection by Complementary Actions of Dendritic Cell Receptor Antagonists and Env-Targeting Virus Inactivators

“…Indeed, 2 h is enough for HIV endocytosis to reach saturation in permissive cell lines, 12 while 24 h is time enough for replication. 13 And in our study the 5-fold increase of HIV RNA associated with cells from 2 h to 24 h might seem a sign of replication. But virus in the infected cells presumably have not replicated because (1) the B-THP-1/DC-SIGN cell line is almost identical to the Raji/DC-SIGN 14 and (2) endocytosis of HIV in Raji/DC-SIGN cells is not observed and they are not permissive to HIV infection.…”

“…12 Inhibitors of HIV infection and transinfection via the DC-SIGN lectin receptor have been tested only in preclinical studies. [13][14][15] Development or application of known drugs for the inhibition of HIV/DC-SIGN interaction may help in decreasing transinfection of T cells and in preventing the infection of DCs that serve as a long-term reservoir of HIV.…”

“…DC-SIGN inhibitors are of special interest as a means of preventing DC infection and CD4 + T cell transinfection by HIV. Many potential DC-SIGN inhibitors are in various stages of research, [13][14][15] and approaches for the high-throughput screening of potential inhibitors are being developed. 37 Our earlier studies on human macrophages 38 demonstrate that dextrans are also inhibitors of the interaction of HIV with another C-type lectin MR (CD206).…”

Broad Antiviral Activity of Carbohydrate-Binding Agents Against Dengue Virus Infection

“…Although DENV has high mannose-type glycans on the E-protein, there was no antiviral activity of AH against DENV infection. Other CBAs such as microvirin, griffithsin and Banlec have been shown to exhibit potent activity against HIV replication [93][94][95], but these CBAs did not show antiviral activity against DENV. Previously, it has been shown that the CBAs HHA, GNA and UDA also target the N-glycans of other viruses, such as HIV, HCV [79] and HCMV [80].…”

Evaluation of the safety and pharmacokinetic profile of the broad spectrum antiviral lectin Griffithsin.

“…and spleens (C) weights were measured relatively to body weight at sacrifice. [29,31,37,142,189,190].…”