Self-Limiting Infection by int/nef-Double Mutants of Simian Immunodeficiency Virus

Vogel, M.; Cichutek, Klaus; Norley, Steve; Kurth, Reinhard

doi:10.1006/viro.1993.1108

Cited by 12 publications

(7 citation statements)

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“…The immediate precursor to the integrated provirus is the linear species. Reports of low-level protein expression from the circular forms of viral DNA (29)(30)(31) are typically overshadowed by evidence that these unique molecules are formed by processes of homologous recombination (one-LTR circular), self-ligation, or autointegration (two-LTR circular) and represent dead-end products of replication (4).…”

Section: Discussionmentioning

confidence: 99%

“…Although studies with HIV-1 have demonstrated that integration is essential for efficient gene expression of retroviral proteins (27), it is possible that transient or low-level expression from unintegrated provirus is involved in retrovirus-induced disease. Previous attempts to demonstrate protein expression from unintegrated retroviral DNA have used integration-incompetent viruses and in vitro systems (29)(30)(31). Similar experiments were considered inappropriate in the current study because of the unavailability of integration-de- fective BLV and because the in vitro behavior of BLV would undoubtedly differ from that which occurs in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to integrating within the host genome, the provirus can exist in both unintegrated linear and circular forms (4). Although limited gene expression from unintegrated retroviral DNA has been reported (29)(30)(31), these proviral species are generally believed to be transcriptionally silent remnants of the viral replication cycle (3,18,22).…”

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confidence: 99%

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Unintegrated bovine leukemia virus DNA: association with viral expression and disease

Reyes

Cockerell

1996

J Virol

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The correlation between bovine leukemia virus (BLV) unintegrated DNA, viral expression, and stage of disease was determined in cattle naturally infected with BLV. The concomitant presence of unintegrated BLV DNA with viral transcriptional activity was observed in 53% (18 of 34) of hematologically normal, BLVseropositive cattle and in 100% (10 of 10) of BLV-seropositive cattle with the preneoplastic syndrome persistent lymphocytosis. In vitro studies suggested that accumulation of unintegrated BLV DNA resulted from a process of reinfection rather than intracellular reverse transcription of newly synthesized BLV RNA. Interestingly, unintegrated BLV DNA was not detected in tumor cells from cattle with BLV-associated lymphocytic leukemia/ malignant lymphoma despite viral transcriptional activity in 100% (eight of eight) of these cattle. Thus, the presence of unintegrated BLV DNA differentiated nonneoplastic from neoplastic conditions in BLV-infected cattle. These results demonstrate that unintegrated viral DNA serves as a marker of disease progression in BLV-infected cattle but is not necessarily associated with induction or maintenance of the neoplastic state.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Unintegrated bovine leukemia virus DNA: association with viral expression and disease

Reyes

Cockerell

1996

J Virol

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“…It also has led to the identification of genes involved in pathogenicity and replication of pathogens, making easier the design of new attenuated vaccines based on targeted modifications of bacterial or viral genomes. 36 Such an approach has been successfully applied to the development of safer attenuated strains, as well as to the design of nonpathogenic live viral vectors able to express and expose heterologous antigens, which can be effectively presented to immune system, eliciting a long-lasting protection with little or no risk of infection at all. 92 Attenuated vaccines and live vectors are often able to replicate in vivo.…”

Section: Live Vectors: Homologous Versus Heterologous Carriers Omentioning

confidence: 99%

“…These reasons make scientists doubtful and worried about new deleted retroviral strains which might prove useful as viral vectors or vaccines. 36 Though deletions have been properly addressed to limit viral infectivity, as well as to impair its replicative capacity or the ability to undergo recombination, the potential effectiveness as vectors and the in vivo safety of these vectors remains to be assessed, both on healthy individuals and those infected with HIV. 37,38 Subunit vaccines, prepared with single or mixed antigens, are a safe way to promote immune response without any risk of nucleic acid contamination.…”

Section: Subunit Vaccinesmentioning

confidence: 99%

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et al. 1997

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Integration of Visna Virus DNA Occurs and May Be Necessary for Productive Infection

List

Haase

1997

Virology

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Proviral integration is thought to be an obligate step of the retroviral replication cycle but the lentivirus visna has been reported to replicate in sheep choroid plexus (SCP) cultures in the absence of proviral integration. Because of new evidence that visna virus has a functional integrase, we reexamined visna virus infection of SCP cultures and found that proviral integration does indeed occur in this setting. While the majority of viral DNA remains unintegrated, integrated proviruses arise early in infection and accumulate over time. The sequences of the resulting host-virus DNA junctions show that, like other retroviruses, visna loses terminal nucleotides from its DNA upon integration. However, unlike other retroviruses, in over half the host-U3 junctions analyzed only a single nucleotide was lost such that the universally conserved CA dinucleotide, two nucleotides from the end of unintegrated viral DNA, did not directly abut host sequences in the provirus. We analyzed the role of integration in visna replication by introducing a series of five mutations into the integrase gene of molecularly cloned visna virus LV1-1KS1. Each mutation abolished viral replication, suggesting that integration may be an obligatory step in replication. We also documented productive infection of SCP cultures in which cell division had been blocked by g-irradiation. The ability of visna to integrate and to replicate in nondividing cells points to the possible utility of visna-based vectors for gene transfer into differentiated cells.

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Self-Limiting Infection by int/nef-Double Mutants of Simian Immunodeficiency Virus

Cited by 12 publications

References 0 publications

Unintegrated bovine leukemia virus DNA: association with viral expression and disease

Unintegrated bovine leukemia virus DNA: association with viral expression and disease

What's going on in vaccine technology?

Integration of Visna Virus DNA Occurs and May Be Necessary for Productive Infection

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