VIRAL IMMUNOLOGY
Volume 23, Number 3, 2010
ª Mary Ann Liebert, Inc.
Pp. 233–234
DOI: 10.1089=vim.2010.ed23.3
Advances in Flavivirus Research
A major feature of this issue of Viral Immunology is
a brace of papers on flaviviruses. The flaviviruses are
single-stranded positive-sense RNA genome viruses that are
transmitted by mosquitoes and ticks. They include many
human pathogens, such as dengue virus (DENV) and yellow
fever virus (YFV), and are responsible for a significant
amount of morbidity and mortality worldwide. Recently, the
National Institute of Allergy and Infectious Diseases
(NIAID) convened a workshop to discuss progress in iden-
tifying flavivirus T- and B-cell epitopes. The goal was to
determine how this information could be used to understand
host-pathogen interactions and develop new vaccines and
diagnostics. Here, Augustine and Repika report on the
workshop and outline the ideas and approaches that were
proposed for future research efforts in this area. One key
proposal was that T- and B-cell epitopes be identified in
flaviviruses for which molecular structures or amino acid
sequences have not yet been defined. In this regard, the
NIAID supports the Immune Epitope Database and Analysis
Resource (IEDB) to provide scientists with immune epitope
information for infectious and immune-mediated diseases.
Due to the clinical significance of flaviviruses, the NIAID
suggested that the IEDB staff conduct a meta-analysis of
flavivirus immune epitopes. This meta-analysis is now
published in this issue of Viral Immunology. Vaughan and
Sette report on 2000 epitopes from over 130 individual
flavivirus-related references identified in PubMed and cu-
rated into the IEDB. The report notes that the majority of the
described epitopes were from DENV and West Nile virus,
presumably because of their impact on human disease, and
the lack of vaccines. This important report will be an in-
valuable tool for Flavivirus researchers.
Two papers in this issue focus on innate immune
responses. Singh and colleagues discuss the role of plasma-
cytoid dendritic cells (pDCs) during early human immuno-
deficiency virus (HIV) infection. The authors show that the
pDC population upregulated apoptotic markers in recent
and advanced HIV infection, and suggest that apoptotic loss
of pDCs may be responsible for impaired innate anti-HIV
immune responses. Interestingly, the presence of function-
ally-competent pDCs in slow progressors implies that these
cells influence the progression of disease. He and colleagues
discuss the role of IFNAR1 genetic polymorphisms on the
long-term pathogenesis of chronic hepatitis B virus (HBV)
infection. The data suggest that the genetic IFNAR1 con-
tributes both to clearance and chronicity at the early stage of
HBV exposure, and persistently influences pathogenesis
during long-term chronic infection.
The relationship between the innate and adaptive immune
responses is complex and involves several levels of regula-
tory interplay. The transcription factor NF-kB plays a key
role in regulating both responses through two major sig-
233
Editorial
naling pathways. Signaling through the classical NF-kB
pathway usually results in the nuclear translocation of
RelA=p50 dimers and regulation of the innate immune re-
sponse. In contrast the alternative NF-kB signaling pathway
involves the RelB=p52 subunits, and results in the regulation
of the adaptive immune response. Planz and colleagues have
now investigated the roles of these pathways in the immune
control of lymphocytic choriomeningitis virus (LCMV).
Using mice that are deficient in NF-kB subunits from either
the classical (p50 = ) or the alternative NF-kB pathway
(p52 = ), the authors show that the alternative NF-kB path-
way is required for the T-cell-mediated immune response
against LCMV. Furthermore, the requirement for the alter-
native NF-kB pathway was manifest at the level of T-cell
priming. Von Herrath and colleagues have analyzed the
T-cell response to LCMV in the context of chronic infection.
The authors note that chronic infections of this nature are
often associated with impaired antiviral CD8 and CD4 T-cell
responses. In addition, they found that CD103, an alpha E
integrin necessary for T-cell homing and retention in the gut
and other epithelia, was upregulated on regulatory T cells
(Tregs) during chronic LCMV infection. However, further
analysis revealed that CD103 expression on Tregs in
chronically-infected mice does not significantly contribute to
T-cell exhaustion. To further understand immune responses
to viral infection, Heidari and colleagues have conducted a
global host gene expression analysis of the chicken response
to Marek’s disease virus (MDV). The study analyzed more
than 32,000 chicken transcripts and most of the known MDV
genes and open reading frames during MDV infection. The
study identified a number of immune-related genes with al-
tered expression levels during infection, and the data should
be invaluable for better understanding the host response to
this virus.
Highly pathogenic H5N1 influenza viruses continue to be
reported, raising concerns that this virus could trigger a
pandemic sometime in the near future. Two articles focus
on the development of vaccines against highly pathogenic
H5N1 influenza viruses. Using a ferret model, Shin and col-
leagues assessed the efficacy of an inactivated H5N1 vaccine
in terms of immune responses and protection from death.
The data suggest that IgG antibodies elicited by the vaccine
may play a major role in protecting ferrets from lethal H5N1
influenza virus challenge. Kositanont and colleagues make
the important observation that cross-neutralizing antibody
against H5N1 virus can be induced after vaccination with
seasonal influenza vaccine. These data suggest that influenza
vaccination, but not influenza virus infection, could induce
cross-neutralizing antibody against avian influenza H5N1
virus.
Also on the vaccine front, Al-Mahtab and colleagues in-
vestigate approaches to control chronic HBV infections in
234
carriers that are at risk of developing liver disease. While
antiviral drugs are not effective or recommended for treat-
ment of these patients, the authors postulate that a combi-
nation therapy of an HBV vaccine and antiviral drugs may
be more effective. Indeed, combination therapy appeared
WOODLAND ET AL.
to be safe, possibly protected against liver damage, and re-
duced HBV DNA levels in all patients. This combination
therapy may be a viable option for the control of HBV in
asymptomatic chronic HBV carriers.
David L. Woodland
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