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2014 ; 25
(4
): 265-84
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Innate immunity to adenovirus
#MMPMID24512150
Hendrickx R
; Stichling N
; Koelen J
; Kuryk L
; Lipiec A
; Greber UF
Hum Gene Ther
2014[Apr]; 25
(4
): 265-84
PMID24512150
show ga
Human adenoviruses are the most widely used vectors in gene medicine, with
applications ranging from oncolytic therapies to vaccinations, but adenovirus
vectors are not without side effects. In addition, natural adenoviruses pose
severe risks for immunocompromised people, yet infections are usually mild and
self-limiting in immunocompetent individuals. Here we describe how adenoviruses
are recognized by the host innate defense system during entry and replication in
immune and nonimmune cells. Innate defense protects the host and represents a
major barrier to using adenoviruses as therapeutic interventions in humans.
Innate response against adenoviruses involves intrinsic factors present at
constant levels, and innate factors mounted by the host cell upon viral
challenge. These factors exert antiviral effects by directly binding to viruses
or viral components, or shield the virus, for example, soluble factors, such as
blood clotting components, the complement system, preexisting immunoglobulins, or
defensins. In addition, Toll-like receptors and lectins in the plasma membrane
and endosomes are intrinsic factors against adenoviruses. Important innate
factors restricting adenovirus in the cytosol are tripartite motif-containing
proteins, nucleotide-binding oligomerization domain-like inflammatory receptors,
and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box
polypeptide 41 and cyclic guanosine monophosphate-adenosine monophosphate
synthase. Adenovirus tunes the function of antiviral autophagy, and counters
innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two
virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing
strategies to engineer adenovirus vectors with attenuated innate responses and
enhanced delivery features.
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