Foamy Virus Transactivation and Gene Expression

Löchelt, Martin

doi:10.1007/978-3-642-55701-9_2

Cited by 38 publications

(49 citation statements)

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“…The provirus genome organization is similar to that of other complex retroviruses, but there are important differences in the way the Pol protein is expressed (3,9,27,51), the nature of the nucleic acid in the virion (25,51), the regulation of gene expression (26), and the structure and function of the Env protein (24). Some of these features would appear to resemble the hepadnavirus replication strategy more closely than that of classical retroviruses (51).…”

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Identification of Domains in Gag Important for Prototypic Foamy Virus Egress

Patton

Morris

Chung

et al. 2005

J Virol

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Sequence motifs (L domains) have been described in viral structural proteins. Mutations in these lead to a defect at a late stage in virus assembly and budding. For several viruses, recruitment of an endosomal sorting complexes required for transport 1 subunit (Tsg101), a component of the class E vacuolar protein sorting (EVPS) machinery, is a prerequisite for virion budding. To effect this, Tsg101 interacts with the PT/SAP L domain. We have identified candidate L-domain motifs, PSAP, PPPI, and YEIL, in the prototypic foamy virus (PFV) Gag protein, based on their homology to known viral L domains. Mutation of the PSAP and PPPI motifs individually reduced PFV egress, and their combined mutation had an additive effect. When PSAP was mutated, residual infectious PFV release was unaffected by dominant negative Vps4 (an ATPase involved in the final stages of budding), and sensitivity to dominant negative Tsg101 was dramatically reduced, suggesting that the PSAP motif functions as a conventional class E VPS-dependent L domain. Consistent with this notion, yeast two-hybrid analysis showed a PSAP motif-dependent interaction between PFV Gag and Tsg101. Surprisingly, PFV release which is dependent on the PPPI motif was Vps4-independent and was partially inhibited by dominant negative Tsg101, suggesting that PPPI functions by an unconventional mechanism to facilitate PFV egress. Mutation of the YEIL sequence completely abolished particle formation and also reduced the rate of Gag processing by the viral protease, suggesting that the integrity of YEIL is required at an assembly step prior to budding and YEIL is not acting as an L domain.

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Identification of Domains in Gag Important for Prototypic Foamy Virus Egress

Patton

Morris

Chung

et al. 2005

J Virol

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“…(i) It enables the virus to differentially regulate its gene expression (16). As described above, FVs accomplish this by using two viral promoters (44).…”

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confidence: 99%

“…The replication pathway of spumaretroviruses diverges in many ways from that of orthoretroviruses (43,61). This aberrant replication strategy also involves the presence of two Tasdependent promoters (8,45,46), differentially regulating the viral gene expression (35,44,61). The internal promoter (IP) is located in the env gene approximately 100 nucleotides upstream of the accessory genes (Fig.…”

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Foamy Virus Nuclear RNA Export Is Distinct from That of Other Retroviruses

Bodem

Schied

Rinaldi

et al. 2011

J Virol

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Most retroviruses express all of their genes from a single primary transcript. In order to allow expression of more than one gene from this RNA, differential splicing is extensively used. Cellular quality control mechanisms retain and degrade unspliced or partially spliced RNAs in the nucleus. Two pathways have been described that explain how retroviruses circumvent this nuclear export inhibition. One involves a constitutive transport element in the viral RNA that interacts with the cellular mRNA transporter proteins NXF1 and NXT1 to facilitate nuclear export. The other pathway relies on the recognition of a viral RNA element by a virus-encoded protein that interacts with the karyopherin CRM1. In this report, we analyze the protein factors required for the nuclear export of unspliced foamy virus (FV) mRNA. We show that this export is CRM1 dependent. In contrast to other complex retroviruses, FVs do not encode an export-mediating protein. Crosslinking experiments indicated that the cellular protein HuR binds to the FV RNA. Inhibition studies showed that both ANP32A and ANP32B, which are known to bridge HuR and CRM1, are essential for FV RNA export. By using this export pathway, FVs solve a central problem of viral replication.The nuclear export of RNA molecules in eukaryotic cells is a tightly regulated process (18,59,63,70,71). Nuclear exit is usually allowed only for fully spliced cellular mRNAs, while intron-containing mRNAs are retained in the nucleus and subsequently degraded (17,18,59,63,70). This defines a specific problem in the replication of retroviruses (RVs), since they must export not only fully spliced but also unspliced or partially spliced mRNAs into the cytoplasm. For the export of the two latter RNA species, retroviruses have found ways to escape both the splicing machinery and the degradation of incompletely spliced mRNAs by making use of either of two strategies for nuclear export of mRNAs with intact splice donor (SD) and acceptor (SA) pairs.In complex retroviruses, such as lentiviruses, some betaretroviruses, and all deltaretroviruses, virus-encoded regulatory proteins (Rev, Rem, and Rex, respectively) bind to the unspliced or incompletely spliced viral mRNA on one hand and contact the karyopherin CRM1 on the other (1,29,33,48,49). Subsequently, this complex shuttles to the cytoplasm, where it delivers the RNA cargo in a regulated fashion that involves Ran in GTP-bound form. Normally CRM1 is used for nuclear export of ribosomal subunits, 5S rRNAs, cellular proteins containing a nuclear export signal (NES), and snRNAs (18,27,53,63). This pathway can also be hitchhiked by endogenous human retroviruses (12,47,74). The presence of regulatory proteins acting at the posttranscriptional level enables complex retroviruses to use a biphasic mode of gene expression ("early" versus "late" phase), resulting in a gain of complexity better known from DNA viruses (16).Alternatively, more simple retroviruses, such as the betaretrovirus Mason-Pfizer monkey virus (MPMV), can (42) contain a cis-acting constitu...

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“…Bet counteracts cellular APOBEC3-mediated restriction and may have a role in particle release and in establishing viral persistence. [72][73][74] Using Bet-gp41 hybrids containing expressing PFV, degeneration of the cerebellar granule cell layer was observed. 62,63 Env proteins of the foamy viruses and virus budding are unique compared with other retroviruses: (1) particle budding strongly depends on co-expression of Env proteins (or compensatory changes in Gag) [64][65][66][67][68][69] and (2) the about 125 aa long leader First immunisation studies with hybrid proteins based on the TM protein of PERV and transplanted MPER and FPPR of gp41 of HIV-1 failed, however by systematic changes in the localization of the grafted gp41 sequences a correct recognition of the 2F5 epitope was achieved.…”

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confidence: 99%

Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

Denner

2013

Human Vaccines & Immunotherapeutics

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Foamy Virus Transactivation and Gene Expression

Cited by 38 publications

References 100 publications

Identification of Domains in Gag Important for Prototypic Foamy Virus Egress

Identification of Domains in Gag Important for Prototypic Foamy Virus Egress

Foamy Virus Nuclear RNA Export Is Distinct from That of Other Retroviruses

Immunising with the transmembrane envelope proteins of different retroviruses including HIV-1

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