Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical.

Abstract:

:Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-alpha/beta) and IFN-gamma receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-alpha/beta receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-gamma receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4(+) T, or CD8(+) T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-alpha/beta is critical for early immune responses to DEN infection, (ii) IFN-gamma-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T- and B-cell-dependent immunity in resistance to primary DEN infection in mice.

journal_name

J Virol

journal_title

Journal of virology

authors

Shresta S,Kyle JL,Snider HM,Basavapatna M,Beatty PR,Harris E

doi

10.1128/jvi.78.6.2701-2710.2004

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

2701-10

issue

6

eissn

0022-538X

issn

1098-5514

journal_volume

78

pub_type

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