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. 2013 Nov 12:10:132.
doi: 10.1186/1742-4690-10-132.

Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription

Alice Assinger, Koon-Chu Yaiw, Ingmar Göttesdorfer, Christine Leib-Mösch, Cecilia Söderberg-Nauclér  1
Affiliations

Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription

Alice Assinger et al. Retrovirology. .

Abstract

Background: Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription.

Findings: Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes.

Conclusions: Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.

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Figures

Figure 1
Figure 1
Effects of HCMV on the activity of Mn2+-dependent RT and HERV transcription profile in human cancer cell lines. A, B: RT activity in glioma initiating cells GliNS1 (A) and G179NS (B) 5 days post infection with 1 MOI HCMV strain VR 1814 or TB40/F; D, E: RT activity in prostate cancer cells PC3 (E) and LNCaP (D); C: RT activity in glioma cell line U373 5 days post infection with 1 MOI HCMV strain VR 1814 or TB40/F; means and standard deviation of 5 independent experiments F: One representative example of false-colour microarray data sets representing uninfected and HCMV - infected (VR 1814, MOI 1, 7 dpi) samples. Detailed information about the identity of microarray capture probes has been described previously [26,27] and can be found in the (Additional file 1). Each positive spot on the microarray represents multiple HERV loci assigned to one subgroup of multicopy HERV elements with sufficient sequence homology. The housekeeping genes upiquitin, GAPD, RPL19 and HPRT served as an internal control. Differences between uninfected and infected cells are indicated by red boxes. **p = <0.01.
Figure 2
Figure 2
Effects of HCMV on the activity of Mn2+-dependent RT and HERV transcription profile in cells from healthy donors. A) RT activity in monocytes from 4 healthy donors (HD1-4) 5 days post infection with 1 MOI HCMV strain VR; B-D: RT activity in HUVEC from 3 healthy donors (I-III) 1–7 days post infection with 1 MOI HCMV strain VR; means and standard deviation of 2 independent infections in triplicates; E: HERV transcription profile of uninfected and HCMV infected HUVECs: One representative example of false-colour microarray data sets representing uninfected and HCMV - infected (VR 1814, MOI 1, 7 dpi) samples. Differences between uninfected and infected cells are indicated by red boxes. For detailed information see Figure 1 and (Additional file 1). **p = <0.01.
Figure 3
Figure 3
Effects of HCMV replication and IE on HERV-K(HML-2) transcription. A) RT activity in glioma initiating cells GliNS1 (A) 7 days post infection with 1 MOI HCMV or UV-inactivated HCMV and filtered HCMV (2 μm pore size); (n = 4); B) Effect of GCV on IEcDNA expression induced by HCMV strain VR 1814 (n = 3) 7 dpi; C) Effect of GCV on HML-2 transcription induced by HCMV strain VR 1814 (n = 3) 7 dpi; D) Effects of siRNA-IE72 and siRNA-IE86 on VR 1814 induced HML-2 transcription (n = 2). E) Effect of HCMV on LINE-1 expression in GliNS1 at 5 and 7 dpi (n = 3). F) Effect of HCMV on HML-2 expression in GliNS1 at 5 and 7 dpi (n = 3). Detailed information on the methods are described in the (Additional file 1). *p = <0.05 **p = <0.01.
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