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Mucosal lymphocytes support latent infections of species C adenoviruses. Because infected lymphocytes resist re-infection with adenovirus, we sought to identify changes in cellular gene expression that could inhibit the infectious process. The expression of over 30,000 genes was evaluated by microarray in persistently infected B-and T-lymphocytic cells. BBS9, BNIP3, BTG3, CXADR, SLFN11 and SPARCL1 were the only genes differentially expressed between mock and infected B cells. Most of these genes are associated with oncogenesis or cancer progression. Histone deacetylase and DNA methyltransferase inhibitors released the repression of some of these genes. Cellular and viral gene expression was compared among leukemic cell lines following adenovirus infection. Childhood leukemic B-cell lines resist adenovirus infection and also show reduced expression of CXADR and SPARCL. Thus adenovirus induces limited changes to infected B-cell lines that are similar to changes observed in childhood leukemic cell lines., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4orf3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4orf3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Human adenovirus can establish latent infections in lymphoid tissues in vivo and persistent, infections in cultured lymphoid cell lines. During lytic infection, adenovirus expresses microRNAs (miRNAs) derived from the viral non-coding RNAs VAI and, especially, VAII. Here, we demonstrate that persistently adenovirus-infected human BJAB cells also produce adenovirus-derived miRNAs primarily derived from the viral VAII RNA, which contributes ~2.7% of all RNA-induced silencing complex (RISC)-associated RNAs. However, our data indicate that the 5' end of the predominant VAII-derived viral RNA, and hence its seed sequence, differs from what has been previously reported. Our data demonstrate that adenovirus expresses viral miRNAs in chronically infected lymphoid cells and raise the possibility that these may contribute to the maintenance of the latently adenovirus-infected lymphoid cells previously observed in mucosal-associated lymphoid tissues in vivo., (© 2013 Elsevier Inc. All rights reserved.)