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Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection.

Vincendeau M, Göttesdorfer I, Schreml JM, Wetie AG, Mayer J, Greenwood AD, Helfer M, Kramer S, Seifarth W, Hadian K, Brack-Werner R, Leib-Mösch C - Retrovirology (2015)

Bottom Line: Analysis of transcripts from individual members of this group revealed up-regulation of predominantly two proviral loci (ERVK-7 and ERVK-15) on chromosomes 1q22 and 7q34 in persistently infected KE37.1 cells, as well as in de novo HIV-1 infected LC5 cells, while only one single HML-2 locus (ERV-K6) on chromosome 7p22.1 was activated in persistently infected LC5 cells.Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production.Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. michelle.vincendeau@helmholtz-muenchen.de.

ABSTRACT

Background: The human genome contains multiple LTR elements including human endogenous retroviruses (HERVs) that together account for approximately 8-9% of the genomic DNA. At least 40 different HERV groups have been assigned to three major HERV classes on the basis of their homologies to exogenous retroviruses. Although most HERVs are silenced by a variety of genetic and epigenetic mechanisms, they may be reactivated by environmental stimuli such as exogenous viruses and thus may contribute to pathogenic conditions. The objective of this study was to perform an in-depth analysis of the influence of HIV-1 infection on HERV activity in different cell types.

Results: A retrovirus-specific microarray that covers major HERV groups from all three classes was used to analyze HERV transcription patterns in three persistently HIV-1 infected cell lines of different cellular origins and in their uninfected counterparts. All three persistently infected cell lines showed increased transcription of multiple class I and II HERV groups. Up-regulated transcription of five HERV taxa (HERV-E, HERV-T, HERV-K (HML-10) and two ERV9 subgroups) was confirmed by quantitative reverse transcriptase PCR analysis and could be reversed by knock-down of HIV-1 expression with HIV-1-specific siRNAs. Cells infected de novo by HIV-1 showed stronger transcriptional up-regulation of the HERV-K (HML-2) group than persistently infected cells of the same origin. Analysis of transcripts from individual members of this group revealed up-regulation of predominantly two proviral loci (ERVK-7 and ERVK-15) on chromosomes 1q22 and 7q34 in persistently infected KE37.1 cells, as well as in de novo HIV-1 infected LC5 cells, while only one single HML-2 locus (ERV-K6) on chromosome 7p22.1 was activated in persistently infected LC5 cells.

Conclusions: Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production. Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material.

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HERV transcription profiles of PMA/ionomycin and CD3/CD28 stimulated Jurkat T-cells. False color mapping was used for image visualization. The house keeping gene HPRT served as a quality control and internal standard. Up-regulated HERV subgroups are indicated by red letters.
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Fig7: HERV transcription profiles of PMA/ionomycin and CD3/CD28 stimulated Jurkat T-cells. False color mapping was used for image visualization. The house keeping gene HPRT served as a quality control and internal standard. Up-regulated HERV subgroups are indicated by red letters.

Mentions: Using RetroArray analysis, the HERV activation pattern of stimulated T-cells was compared with that obtained after HIV-1 infection (Figure 7 and 2). A variety of HERV groups derived from all three HERV classes was found to be up-regulated after addition of both stimuli, PMA/Ionomycin and CD3/CD28 (Figure 7). Interestingly, the transcription pattern in stimulated T-cells includes HERV groups also affected in de novo (HERV-E, ERV9, HERV-K (HML-2), HERV-K (HML-3)) as well as in persistently HIV-1 infected cells (HERV-T, ERV9, HERV-K (HML-3), HERV-K (HML-4), HERV-K (HML-10)). Since IL2 is a major target of the transcription factors induced by PMA/Ionomycin or CD3/CD28, we verified successful stimulation of the cells by measuring IL2 mRNA (Additional file 6). The data suggests that major transcription factors like NF-κB, NFAT and AP1 may be involved in the activation of at least some HERV taxa in HIV-1 infected cells.Figure 7


Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection.

Vincendeau M, Göttesdorfer I, Schreml JM, Wetie AG, Mayer J, Greenwood AD, Helfer M, Kramer S, Seifarth W, Hadian K, Brack-Werner R, Leib-Mösch C - Retrovirology (2015)

HERV transcription profiles of PMA/ionomycin and CD3/CD28 stimulated Jurkat T-cells. False color mapping was used for image visualization. The house keeping gene HPRT served as a quality control and internal standard. Up-regulated HERV subgroups are indicated by red letters.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4375885&req=5

Fig7: HERV transcription profiles of PMA/ionomycin and CD3/CD28 stimulated Jurkat T-cells. False color mapping was used for image visualization. The house keeping gene HPRT served as a quality control and internal standard. Up-regulated HERV subgroups are indicated by red letters.
Mentions: Using RetroArray analysis, the HERV activation pattern of stimulated T-cells was compared with that obtained after HIV-1 infection (Figure 7 and 2). A variety of HERV groups derived from all three HERV classes was found to be up-regulated after addition of both stimuli, PMA/Ionomycin and CD3/CD28 (Figure 7). Interestingly, the transcription pattern in stimulated T-cells includes HERV groups also affected in de novo (HERV-E, ERV9, HERV-K (HML-2), HERV-K (HML-3)) as well as in persistently HIV-1 infected cells (HERV-T, ERV9, HERV-K (HML-3), HERV-K (HML-4), HERV-K (HML-10)). Since IL2 is a major target of the transcription factors induced by PMA/Ionomycin or CD3/CD28, we verified successful stimulation of the cells by measuring IL2 mRNA (Additional file 6). The data suggests that major transcription factors like NF-κB, NFAT and AP1 may be involved in the activation of at least some HERV taxa in HIV-1 infected cells.Figure 7

Bottom Line: Analysis of transcripts from individual members of this group revealed up-regulation of predominantly two proviral loci (ERVK-7 and ERVK-15) on chromosomes 1q22 and 7q34 in persistently infected KE37.1 cells, as well as in de novo HIV-1 infected LC5 cells, while only one single HML-2 locus (ERV-K6) on chromosome 7p22.1 was activated in persistently infected LC5 cells.Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production.Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. michelle.vincendeau@helmholtz-muenchen.de.

ABSTRACT

Background: The human genome contains multiple LTR elements including human endogenous retroviruses (HERVs) that together account for approximately 8-9% of the genomic DNA. At least 40 different HERV groups have been assigned to three major HERV classes on the basis of their homologies to exogenous retroviruses. Although most HERVs are silenced by a variety of genetic and epigenetic mechanisms, they may be reactivated by environmental stimuli such as exogenous viruses and thus may contribute to pathogenic conditions. The objective of this study was to perform an in-depth analysis of the influence of HIV-1 infection on HERV activity in different cell types.

Results: A retrovirus-specific microarray that covers major HERV groups from all three classes was used to analyze HERV transcription patterns in three persistently HIV-1 infected cell lines of different cellular origins and in their uninfected counterparts. All three persistently infected cell lines showed increased transcription of multiple class I and II HERV groups. Up-regulated transcription of five HERV taxa (HERV-E, HERV-T, HERV-K (HML-10) and two ERV9 subgroups) was confirmed by quantitative reverse transcriptase PCR analysis and could be reversed by knock-down of HIV-1 expression with HIV-1-specific siRNAs. Cells infected de novo by HIV-1 showed stronger transcriptional up-regulation of the HERV-K (HML-2) group than persistently infected cells of the same origin. Analysis of transcripts from individual members of this group revealed up-regulation of predominantly two proviral loci (ERVK-7 and ERVK-15) on chromosomes 1q22 and 7q34 in persistently infected KE37.1 cells, as well as in de novo HIV-1 infected LC5 cells, while only one single HML-2 locus (ERV-K6) on chromosome 7p22.1 was activated in persistently infected LC5 cells.

Conclusions: Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production. Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material.

Show MeSH
Related in: MedlinePlus