Next Article in Journal
Porcine Epidemic Diarrhea Virus (PEDV) ORF3 Enhances Viral Proliferation by Inhibiting Apoptosis of Infected Cells
Previous Article in Journal
Selective Reactivity of Anti-Japanese Encephalitis Virus NS4B Antibody Towards Different Flaviviruses
Open AccessArticle

Characterization of Adenovirus 5 E1A Exon 1 Deletion Mutants in the Viral Replicative Cycle

1
Department of Microbiology, University of Manitoba, 45 Chancellor’s Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada
2
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(2), 213; https://doi.org/10.3390/v12020213
Received: 8 January 2020 / Revised: 10 February 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
(This article belongs to the Section Animal Viruses)
Human adenovirus infection is driven by Early region 1A (E1A) proteins, which are the first proteins expressed following the delivery of the viral genome to the cellular nucleus. E1A is responsible for reprogramming the infected cell to support virus replication alongside the activation of expression of all viral transcriptional units during the course of the infection. Although E1A has been extensively studied, most of these studies have focused on understanding the conserved region functions outside of a full infection. Here, we investigated the effects of small deletions in E1A exon 1 on the viral replicative cycle. Almost all deletions were found to have a negative impact on viral replication with the exception of one deletion found in the mutant dl1106, which replicated better than the wild-type E1A expressing dl309. In addition to growth, we assessed the virus mutants for genome replication, induction of the cytopathic effect, gene and protein expression, sub-cellular localization of E1A mutant proteins, induction of cellular S-phase, and activation of S-phase specific cellular genes. Importantly, our study found that virus replication is likely limited by host-specific factors, rather than specific viral aspects such as the ability to replicate genomes or express late proteins, after a certain level of these has been expressed. Furthermore, we show that mutants outside of the conserved regions have significant influence on viral fitness. Overall, our study is the first comprehensive evaluation of the dl1100 series of exon 1 E1A deletion mutants in viral fitness and provides important insights into the contribution that E1A makes to viral replication in normal human cells.
Keywords: adenovirus; E1A; exon 1; replication adenovirus; E1A; exon 1; replication
Show Figures

Graphical abstract

MDPI and ACS Style

Costa, R.; Akkerman, N.; Graves, D.; Crisostomo, L.; Bachus, S.; Pelka, P. Characterization of Adenovirus 5 E1A Exon 1 Deletion Mutants in the Viral Replicative Cycle. Viruses 2020, 12, 213.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop