Identification of late assembly domains of the human endogenous retrovirus-K(HML-2)

Chudak, Claudia; Beimforde, Nadine; George, Maja; Zimmermann, Anja; Lausch, Veronika; Hanke, Kirsten; Bannert, Norbert

doi:10.1186/1742-4690-10-s1-p4

Cited by 2 publications

(8 citation statements)

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“…The generation of pBSK-oriHERV-K113 (“oriHERV-K113”) has been described elsewhere [ 11 ]. Briefly, the proviral sequence of HERV-K113 (GenBank AY037928) was amplified from the RP11-12X BAC-library plasmid [ 14 ] and cloned into the pBlueskript SK+ (pBSK) vector (Agilent Technologies, Inc., Cedar Creek, NE, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Such recombination events reconstituting functional proviruses from inactivated endogenous elements would not be without precedence and have already been documented in animals [ 9 , 10 ]. A plethora of knowledge concerning the basic biology of HERV-K(HML2) and various aspects of the virus/host interaction has recently been obtained by expressing engineered consensus sequences and a reconstituted HERV-K113 element (oriHERV-K113) in which synonymous post-insertional mutations have been reverted [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this current study we generated and expressed a CMV-promoter driven and partially codon-optimized version of a reconstituted HERV-K113 molecular clone (oriHERV-K113) described previously [ 11 ]. In comparison to oriHERV-K113, high expression of the codon optimized variant (termed oricoHERV-K113) lead to an unexpected switch from a C-type to an A-type-like morphology, as demonstrated by thin-section electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

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CMV-Promoter Driven Codon-Optimized Expression Alters the Assembly Type and Morphology of a Reconstituted HERV-K(HML-2)

Hohn

Hanke

Lausch

et al. 2014

Viruses

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The HERV-K(HML-2) family contains the most recently integrated and best preserved endogenized proviral sequences in the human genome. All known elements have nevertheless been subjected to mutations or deletions that render expressed particles non-infectious. Moreover, these post-insertional mutations hamper the analysis of the general biological properties of this ancient virus family. The expression of consensus sequences and sequences of elements with reverted post-insertional mutations has therefore been very instrumental in overcoming this limitation. We investigated the particle morphology of a recently reconstituted HERV-K113 element termed oriHERV-K113 using thin-section electron microscopy (EM) and could demonstrate that strong overexpression by substitution of the 5'LTR for a CMV promoter and partial codon optimization altered the virus assembly type and morphology. This included a conversion from the regular C-type to an A-type morphology with a mass of cytoplasmic immature cores tethered to the cell membrane and the membranes of vesicles. Overexpression permitted the release and maturation of virions but reduced the envelope content. A weaker boost of virus expression by Staufen-1 was not sufficient to induce these morphological alterations.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CMV-Promoter Driven Codon-Optimized Expression Alters the Assembly Type and Morphology of a Reconstituted HERV-K(HML-2)

Hohn

Hanke

Lausch

et al. 2014

Viruses

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“…New and exciting opportunities for a general functional and structural characterization of HML‐2 biology that largely solve the aforementioned problem have been made available by the generation and expression of HML‐2 consensus sequences and the identification and reversion of postinsertional mutations in sequences and molecular clones . Using HML‐2 consensus sequences, it was demonstrated that the ancient virus is still able to gain entry into the cytoplasm of a cell, to complete reverse transcription, and to integrate into the genome of the infected host cell by a retrovirus‐typical target site duplication .…”

Section: Reconstitution and Expression Of Hml‐2 Sequences And What Wementioning

confidence: 99%

“…Resurrected HML‐2 sequences and molecular clones are also very instrumental for analyzing events at later stages of the replication cycle. Using oriHERV‐K113, a molecular clone of HERV‐K113 with reconstituted non‐synonymous postinsertional mutations, we have identified and analyzed the late domains of HML‐2 that play an important role during the egress of particles from the cell . We found that a consensus PTAP‐motif in the p15 Gag protein forms the core of a major late domain of the virus and two YPX(n)L motifs serve as auxiliary late domains.…”

Section: Reconstitution and Expression Of Hml‐2 Sequences And What Wementioning

confidence: 99%

HERV‐K(HML‐2), a seemingly silent subtenant – but still waters run deep

Hanke

Hohn

Bannert

2016

APMIS

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A large proportion of the human genome consists of endogenous retroviruses, some of which are well preserved, showing transcriptional activity, and expressing retroviral proteins. The HERV‐K(HML‐2) family represents the most intact members of these elements, with some having open and intact reading frames for viral proteins and the ability to form virus‐like particles. Although generally suppressed in most healthy tissues by a variety of epigenetic processes and antiviral mechanisms, there is evidence that some members of this family are (at least partly) still active – particularly in certain stem cells and various tumors. This raises the possibility of their involvement in tumor induction or in developmental processes. In recent years, many new insights into this fascinating field have been attained, and this review focuses on new discoveries about coevolutionary events and intracellular defense mechanisms against HERV‐K(HML‐2) activity. We also describe what might occur when these mechanisms fail or become modulated by viral proteins or other viruses and discuss the new vistas opened up by the reconstitution of ancestral viral proteins and even complete HML‐2 viruses.

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Identification of late assembly domains of the human endogenous retrovirus-K(HML-2)

Cited by 2 publications

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CMV-Promoter Driven Codon-Optimized Expression Alters the Assembly Type and Morphology of a Reconstituted HERV-K(HML-2)

CMV-Promoter Driven Codon-Optimized Expression Alters the Assembly Type and Morphology of a Reconstituted HERV-K(HML-2)

HERV‐K(HML‐2), a seemingly silent subtenant – but still waters run deep

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