Antibodies against immature virions are not a discriminating factor for dengue disease severity.

Abstract:

:Humoral immunity plays an important role in controlling dengue virus (DENV) infection. Antibodies (Abs) developed during primary infection protect against subsequent infection with the same dengue serotype, but can enhance disease following secondary infection with a heterologous serotype. A DENV virion has two surface proteins, envelope protein E and (pre)-membrane protein (pr)M, and inefficient cleavage of the prM protein during maturation of progeny virions leads to the secretion of immature and partially immature particles. Interestingly, we and others found that historically regarded non-infectious prM-containing DENV particles can become highly infectious in the presence of E- and prM-Abs. Accordingly, we hypothesized that these virions contribute to the exacerbation of disease during secondary infection. Here, we tested this hypothesis and investigated the ability of acute sera of 30 DENV2-infected patients with different grades of disease severity, to bind, neutralize and/or enhance immature DENV2. We found that a significant fraction of serum Abs bind to the prM protein and to immature virions, but we observed no significant difference between the disease severity groups. Furthermore, functional analysis of the Abs did not underscore any specific correlation between the neutralizing/enhancing activity towards immature DENV2 and the development of more severe disease. Based on our analysis of acute sera, we conclude that Abs binding to immature virions are not a discriminating factor in dengue pathogenesis.

journal_name

PLoS Negl Trop Dis

authors

Rodenhuis-Zybert IA,da Silva Voorham JM,Torres S,van de Pol D,Smit JM

doi

10.1371/journal.pntd.0003564

subject

Has Abstract

pub_date

2015-03-11 00:00:00

pages

e0003564

issue

3

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-14-01104

journal_volume

9

pub_type

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