Antibodies that block virus attachment to vero cells are a major component of the human neutralizing antibody response against dengue virus type 2

Abstract

Epidemiological data strongly implicate a role for the host humoral immune response in both protection against and exacerbation of dengue virus-caused disease. In an effort to characterize elements of the normal human immune response against dengue virus we have addressed the issue of antibody-mediated neutralization of dengue virus. We show here the ability of both mouse monoclonal antibody 3H5 and human anti-dengue neutralizing sera to block binding of dengue-2 virus to monkey kidney (Vero) cells. Since Vero cells possess virus receptors but not Fc receptors we conclude that the major effect of host neutralizing antibodies is to block virus attachment to Vero cell dengue virus receptors. Analysis of 61 patient antisera yielded good correlation (Pearson's coefficient = 0.90; P < 0.001) between neutralizing activity and ability to block virus-cell attachment suggesting that antibody-mediated neutralization of dengue virus occurs primarily extracellularly and less by a postattachment mechanism as has been described for certain other viruses.

Histidine 39 in the dengue virus type 2 M protein has an important role in virus assembly

“…In our experiments, the levels of secreted prM were high relative to intracellular prM levels, both from virally infected C6/36 cells and from pSVprM-E-transfected COS cells, suggesting that prM processing was impaired. Similarly, infectious DENV particles with a high proportion of prM have consistently been found to be released from infected cells (Anderson et al, 1997;He et al, 1995;Henchal et al, 1985;Murray et al, 1993;Putnak et al, 1996;Randolph & Stollar, 1990;Roehrig et al, 1998;Wang et al, 1999). Recent studies mutating the prM furin cleavage site of TBEV (Elshuber et al, 2003) and DENV-2 (Keelapang et al, 2004) have shown that, whilst cleavage of prM is essential for virus infectivity, enhanced furin cleavage of the DENV prM protein affects virus export adversely, suggesting that it may be advantageous for DENV to retain some prM on the virus surface.…”

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

“…4). Blocking of cell surface attachment or receptor engagement through steric hindrance may be a common mechanism and has been suggested to explain the activity of DENVimmune sera (176). However, many antibodies are also capable of blocking infection at a postattachment step (51,59,167,(177)(178)(179).…”

Unmutated immunoglobulin M can protect mice from death by influenza virus infection

“…Prevention of viral infection by antibodies depends on diverse mechanisms such as prevention of viral attachment to the host cell (1,2), activation of the complement system (3,4), opsonization (5), antibody-dependent cell-mediated cytotoxicity (6,7), and inhibition of the release of daughter viruses from infected cells (8)(9)(10). Such a wide variety of antibody activities are mediated by a generation of various classes of antibody (IgG, IgA, and IgE) besides IgM and IgD through class switch recombination (CSR; 11).…”