Reverse Transcriptase Jumps and Gaps

Kupiec, Jean-Jacques; Sonigo, Pierre

doi:10.1099/0022-1317-77-9-1987

Cited by 23 publications

(14 citation statements)

References 37 publications

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“…Between the PBS and the first Met residue of Gag, the SI region as well as the palindromic SII sequence ([A/T]TCCCTAGGG[T/A]), which have been implicated in HFV RNA dimerization in vitro, are completely conserved in EFV, demonstrating their importance among this viral family. A sequence located at the 3Ј end of pol (nt 7004 to 7013) consists of a duplication of the 3Ј PPT (AAGGAGAGGG, nt 10577 to 10586) and may represent the central PPT used for positive-strand DNA synthesis (9).…”

Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of an Equine Foamy Virus

Tobaly-Tapiero

Bittoun

Neves

et al. 2000

J Virol

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Foamy viruses (FVs) are complex retroviruses which have been isolated from different animal species including nonhuman primates, cattle, and cats. Here, we report the isolation and characterization of a new FV isolated from blood samples of horses. Similar to other FVs, the equine foamy virus (EFV) exhibits a highly characteristic ultrastructure and induces syncytium formation and subsequent cell lysis on a large number of cell lines. Molecular cloning of EFV reveals that the general organization is that of other known FVs, whereas sequence similarity with its bovine FV counterpart is only 40%. Interestingly, EFV buds exclusively from the plasma membrane and not from the endoplasmic reticulum (ER), as previously shown for other FVs. The absence of the ER retrieval dilysine motif in EFV Env is likely responsible for this unexpected sorting pathway.Foamy viruses (FVs), also known as spumaviruses, are widespread complex retroviruses which have been isolated from nonhuman primates, cattle, and cats. Although highly lytic in vitro, these viruses, which are innocuous in vivo, are known to induce a persistent infection in their hosts (20). All FVs characterized to date have very large genomes (between 12 to 13 kb) with the classical gag, pol, and env structural genes and additional regulatory open reading frames (ORFs) located at the 3Ј end of the env gene which are under the control of both the 5Ј long terminal repeat (LTR) and an internal promoter (IP) (14). In the case of the human foamy virus (HFV), the prototype FV, two accessory proteins, Tas and Bet, have been described. While Tas (originally called Bel1) is the potent DNA binding transactivator of viral gene expression of both the LTR and the IP, Bet has been shown to play a key role in the establishment and control of viral persistence in vitro (1,19).The molecular biology of retroviruses was highly focused on human T-cell leukemia virus (HTLV) and human immunodeficiency virus (HIV), clearly associated with human pathologies. However, recent findings regarding FVs raise important issues of general interest. Indeed, some of their features, such as the formation of a specific pol mRNA and the infectivity of the incoming viral DNA contained in extracellular virions (26, 28), set FVs apart from all other retroviruses. By virtue of these two features, FVs resemble pararetroviruses.By analogy with lentiviruses, which were isolated from cattle, cats, primates, goats, and horses, we decided to look for the presence of an FV in horses. Here, we report the isolation of a new nonprimate FV from blood samples of naturally infected horses. The equine foamy virus (EFV) has been characterized by molecular cloning and nucleotide sequence analysis. The ultrastructure of the extracellular virion and the genomic organization were investigated and compared to those of other cloned FVs. Although displaying limited sequence similarities with primate FVs, EFV is phylogenetically closer to nonprimate FVs, especially to the bovine foamy virus (BFV). Interestingly, in contrast to other...

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Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of an Equine Foamy Virus

Tobaly-Tapiero

Bittoun

Neves

et al. 2000

J Virol

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“…Visna and HIV-1, and human/simian spumaviruses as well, contain an exact copy of their respective PPTs in pol [110,111]. In the pre-integration complexes of these viruses, a plusstrand gap corresponding to a second site of plus-strand initiation has been detected at this central PPT (cPPT) [105,106,[112][113][114][115][116][117]. The net outcome is that the plus strand of the PIC contains two discrete half-genomic DNA segments.…”

Section: Mechanisms Of Lentiviral Nuclear Import: Central Dna Flaps Amentioning

confidence: 99%

FIV: from lentivirus to lentivector

Saenz

Poeschla

2004

J. Gene Med.

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SummaryMolecular virological understanding of the feline immunodeficiency virus (FIV) life cycle is increasing, facilitating rational derivation of improved vectors from this non-primate lentivirus. The packaging signal has been mapped, a central DNA flap has been identified, and class I integrase mutants have been validated. Vector systems with improved effectiveness and safety profiles are being applied by a number of laboratories in several pre-clinical models, with demonstrated efficacy in human tissues. The comparative lentivirological research that facilitates FIV vector development may also yield insights into the still enigmatic molecular basis for a signature lentiviral property with pathogenetic and therapeutic importance: permanent transgene integration in non-dividing cells. This review discusses virological aspects of lentiviral vector development, as well as some recent controversies and applications.

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“…In the infected cell, spumaviruses accumulate multiple copies of unintegrated linear double-stranded DNA harboring a gap in the positive strand (2,12). In most retroviruses, circular DNAs, harboring one or two long terminal repeats (LTRs), are thought to form in the nucleus, either from homologous recombination between the two LTRs or from intramolecular ligation (3,5,10,18,19,22,23).…”

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confidence: 99%

Biphasic DNA Synthesis in Spumaviruses

Delelis

Saı̈b

Sonigo

2003

J Virol

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Spumaviruses are complex retroviruses whose replication cycle resembles that of hepadnaviruses, especially by a late-occurring reverse transcription step. The possible existence of an early reverse transcription as observed in other retroviruses was not documented. Using real-time quantitative PCR, we addressed directly the kinetics of DNA synthesis during spumavirus infection. An early phase of viral DNA synthesis developed until 3 h postinfection, followed by a second phase, culminating 10 h postinfection. Both phases were abolished by the reverse transcriptase inhibitor 3-azido-3-deoxythymidine. Similar to other retroviruses, circular forms of viral DNA harboring two long terminal repeats were mainly found in the nucleus of infected cells. Interestingly, a fraction of these circular forms were detected in the cytoplasm and in extracellular virions, a feature shared with hepadnaviruses. Combined with packaging of both viral DNA and RNA genomes in virions, early and late reverse transcription might allow spumavirus to maximize its genome replication.

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Reverse Transcriptase Jumps and Gaps

Cited by 23 publications

References 37 publications

Isolation and Characterization of an Equine Foamy Virus

Isolation and Characterization of an Equine Foamy Virus

FIV: from lentivirus to lentivector

Biphasic DNA Synthesis in Spumaviruses

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