Accumulation of specific RNAs encoding transcriptional factors and stress response proteins against a background of severe depletion of cellular RNAs in cells infected with herpes simplex virus 1 - PubMed (original) (raw)

Accumulation of specific RNAs encoding transcriptional factors and stress response proteins against a background of severe depletion of cellular RNAs in cells infected with herpes simplex virus 1

N N Khodarev et al. Proc Natl Acad Sci U S A. 1999.

Abstract

Herpes simplex virus 1 encodes several functions to preclude the shutoff of host response to infection, including degradation of mRNA immediately after infection. To determine whether any cellular mRNAs accumulate in infected cells against a background of severe loss of host RNA, we hybridized cDNAs derived from three different cell lines infected with wild type and a mutant virus to a DNA array containing probes for 588 human genes representing different functional groups. The results were that (i) infected cells accumulated at levels above those of mock-infected cells, a small number of transcripts representing transcriptional factors that could regulate gene expression both positively and negatively, and one stress response protein (GADD45), (ii) the amount and nature of the accumulated transcripts showed limited variability depending on the cell and virus, and (iii) at least some of the proteins encoded by the accumulated transcripts could benefit either the virus or the host.

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Figures

Figure 1

Figure 1

Autoradiographic images of DNA arrays probed with cDNA obtained from HLF mock-infected (Top), infected with the recombinant virus R3616 (Middle), or parent, wild-type virus HSV-1(F) (Bottom). Genes probes are grouped into quadrants as follows: (A) control of cell cycle; (B) signal transduction; (C) apoptosis and DNA repair; (D) transcriptional factors; (E) receptors and cell adhesion; and (F) cytokines and hormones.

Figure 2

Figure 2

Autoradiographic images from quadrant C containing probes representing genes involved in apoptosis, stress, and DNA repair probed with cDNA obtained from HLF, U87-lux8, and U87–175.4 cells mock-infected or infected with R3616 or HSV-1(F) for 5 hr. The white box surrounds the location of GADD45 (upper two dots) and GADD153 (lower two dots).

Figure 3

Figure 3

Autoradiographic images of quadrant D containing probes representing genes encoding regulatory proteins and transcription factors. The DNA arrays were probed with cDNA obtained from HLF, U87-lux8, and U87–175.4 cells mock-infected or infected with R3616 or HSV-1(F) for 5 hr. mRNA species that accumulated in HSV-1-infected cells are boxed in white and numbered as follows: 1, tristetraprolin; 2, ATF-4; 3, Egr1; 4, ETR101; 5, HOX7; and 6, Id-2. mRNAs that accumulated specifically U87–175.4 cells infected with R3616 in contrast to mock-infected cells or cells infected with HSV-1(F) infection in are marked by dashed boxes boxed and labeled as follows: 7, AP-2; 8, CCAAT DNA box-binding protein; and 9, Id-3.

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