Clinical features and treatment of adenovirus infections

Lenaerts, Liesbeth; Clercq, Erik De; Naesens, Lieve

doi:10.1002/rmv.589

Cited by 209 publications

(204 citation statements)

References 146 publications

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“…Although these diseases are self-limiting in immunocompetent individuals, they cause significant morbidity in AIDS, cancer, and organ transplant patients with compromised immune systems (2)(3)(4). Because of their broad cell tropism and ease of genome manipulation, replication-deficient or conditionally replicating HAdVs are also being evaluated in the clinic as potential vaccine and gene therapy vectors (5).…”

mentioning

confidence: 99%

Structures and organization of adenovirus cement proteins provide insights into the role of capsid maturation in virus entry and infection

Reddy¹,

Nemerow

2014

Proc. Natl. Acad. Sci. U.S.A.

118

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Adenovirus cement proteins play crucial roles in virion assembly, disassembly, cell entry, and infection. Based on a refined crystal structure of the adenovirus virion at 3.8-Å resolution, we have determined the structures of all of the cement proteins (IIIa, VI, VIII, and IX) and their organization in two distinct layers. We have significantly revised the recent cryoelectron microscopy models for proteins IIIa and IX and show that both are located on the capsid exterior. Together, the cement proteins exclusively stabilize the hexon shell, thus rendering penton vertices the weakest links of the adenovirus capsid. We describe, for the first time to our knowledge, the structure of protein VI, a key membrane-lytic molecule, and unveil its associations with VIII and core protein V, which together glue peripentonal hexons beneath the vertex region and connect them to the rest of the capsid on the interior. Following virion maturation, the cleaved N-terminal propeptide of VI is observed, reaching deep into the peripentonal hexon cavity, detached from the membrane-lytic domain, so that the latter can be released. Our results thus provide the molecular basis for the requirement of maturation cleavage of protein VI. This process is essential for untethering and release of the membrane-lytic region, which is known to mediate endosome rupture and delivery of partially disassembled virions into the host cell cytoplasm.human adenovirus | cement protein scaffold | structure-function relationships H uman adenoviruses (HAdVs) are large (∼150 nm in diameter, 150-MDa) nonenveloped double-stranded DNA (dsDNA) viruses that cause respiratory, ocular, and enteric diseases (1). Although these diseases are self-limiting in immunocompetent individuals, they cause significant morbidity in AIDS, cancer, and organ transplant patients with compromised immune systems (2-4). Because of their broad cell tropism and ease of genome manipulation, replication-deficient or conditionally replicating HAdVs are also being evaluated in the clinic as potential vaccine and gene therapy vectors (5).The capsid shell of an adenovirus (Ad) comprises multiple copies of three major capsid proteins (MCPs; hexon, penton base, and fiber) and four minor/cement proteins (IIIa, VI, VIII, and IX) that are organized with pseudo-T = 25 icosahedral symmetry ( Fig. 1 A and B). In addition, six other proteins (V, VII, μ, IVa2, terminal protein, and adenovirus protease) are encapsidated along with the 36-kb dsDNA genome inside the capsid (Fig. 1A). The crystal structures of all three MCPs are known, and so is their organization in the capsid from prior X-ray crystallography (6-8) and cryoelectron microscopy (cryo-EM) analyses (9, 10). Recently, high-resolution structures of recombinant HAdV5 vectors have been determined using cryo-EM (11) and X-ray methods (12) that revealed the structures and organization of some of the cement proteins. Both studies agree closely on the organization of the MCPs and confirm the earlier cryo-EM observations (9, 10, 13), but neither provided...

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mentioning

confidence: 99%

Structures and organization of adenovirus cement proteins provide insights into the role of capsid maturation in virus entry and infection

Reddy¹,

Nemerow

2014

Proc. Natl. Acad. Sci. U.S.A.

118

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“…Sporadically, HAdVs can cause viral meningitis, encephalitis or hemorrhagic cystitis. 19 Because of its association with mild disease and a relatively easy to manipulate genome (as compared to other HAdV types/ species), most work on HAdV as vector for (cancer) gene therapy has been done with serotype 5 of species C. HAdVs have distinct advantages as a gene transfer vector, including high transfection efficiency of cells irrespective of their growth status. The genome of HAdVs is easy to manipulate for retargeting and insertion of transgenes, and efficient production of high titer virus stocks is possible.…”

Section: Family Herpesviridae: Herpes Simplex Virus 1 (Hsv)mentioning

confidence: 99%

Oncolytic viruses: From bench to bedside with a focus on safety

Buijs

Verhagen

Eijck

et al. 2015

Human Vaccines & Immunotherapeutics

107

105

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“…It is important that early detection of Adenoviremia enables us to initiate therapy before a significant increase in mortality (La Rosa et al, 2001). Although less efficient than Cidofovir or Ribavirin, Ganciclovir can interfere with the function of adenovirus DNA polymerase, thus inhibiting viral replication in vitro (Lenaerts et al, 2008). In retrospective studies, lower incidences of adenovirus infections appeared to be reported in patients treated with Ganciclovir as cytomegalovirus prophylaxis (Bruno et al, 2003).…”

Section: Treatment To Avoid Hemodialysis Before and During Hemorrhagimentioning

confidence: 99%