Controlling Herpes Simplex Virus Infections: is Intracellular Immunization the Way of the Future?

Wong, K. K.; Chatterjee, Som S.

doi:10.1007/978-3-642-77247-4_10

Cited by 5 publications

(2 citation statements)

References 91 publications

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“…To accomplish this goal, we have employed intracellular immunization, i.e., the regulated expression of a molecular species designed to interfere with and prevent HIV-1 replication (4). In order to be effective, the introduced genes must (i) be stably expressed in sufficient quantities to inhibit viral replication, (ii) be nontoxic to the target cells, and (iii) be efficiently transferred to the target cells (60). The intracellular immunization approach used in the current study selectively expresses PKR following HIV-1 reactivation.…”

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confidence: 99%

Inhibition of Replication of Reactivated Human Immunodeficiency Virus Type 1 (HIV-1) in Latently Infected U1 Cells Transduced with an HIV-1 Long Terminal Repeat-Driven PKR cDNA Construct

Muto¹,

Martinand‐Mari

Adelson³

et al. 1999

J Virol

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Treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals with highly active antiretroviral therapy has effectively decreased viral load to undetectable levels. However, efforts to eliminate HIV-1 from these individuals have been unsuccessful, due to the presence of stable, latent viral reservoirs in resting and active CD4+ T lymphocytes and macrophages. These latent populations have become critical targets in the effort to eradicate HIV-1 from infected individuals. The mechanisms of HIV-1 latency have been studied by using the HIV-1-infected promonocytic cell line U1. The interferon-inducible double-stranded RNA-dependent p68 protein kinase (PKR), a key enzyme in the host-mediated antiviral response, is known to be down-regulated during HIV-1 infection. Therefore, in order to evaluate the role of PKR in the inhibition of replication of reactivated HIV-1 in latently infected U1 cells, we have utilized cDNA constructs containing PKR under the transcriptional control of the HIV-1 long terminal repeat. One PKR-transduced clone, U1/106-4:27, inhibited the tumor necrosis factor alpha (TNF-α)-induced replication of HIV-1 by 99% compared to control U1 cells as measured by syncytium formation and HIV-1 p24 antigen enzyme-linked immunosorbent assay. Western blot analysis showed an increase in PKR expression through 96 h postinduction in the U1/106-4:27 clone, concomitant with maximal increases in phosphorylation of the α subunit of eukaryotic initiation factor 2 and NF-κB activity at 72 h postinduction. These results demonstrate that overexpression of PKR can inhibit the replication of reactivated HIV-1 in latently infected cells and confirm the involvement of PKR in the interferon-associated antiviral pathway against HIV-1 infection. Additionally, treatment of the PKR-transduced U1/106-4:27 clone with the protease inhibitor saquinavir (250 nM) completely inhibited TNF-α-induced HIV-1 replication.

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confidence: 99%

Inhibition of Replication of Reactivated Human Immunodeficiency Virus Type 1 (HIV-1) in Latently Infected U1 Cells Transduced with an HIV-1 Long Terminal Repeat-Driven PKR cDNA Construct

Muto¹,

Martinand‐Mari

Adelson³

et al. 1999

J Virol

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“…Vaccination of pigs with the chimeric virus resulted in a protective immune response against both viruses, demonstrating the potency of PRV as a viral vector. Other potential applications of attenuated viruses are delivery of heterologous genes in specific cells to complement genetic defects (13), to kill deranged cells (11), or to interfere with the replication of pathogens (2,45). The use of herpesviruses like PRV to introduce foreign DNA into cells has a number of attractive advantages.…”

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confidence: 99%

Construction and properties of pseudorabies virus recombinants with altered control of immediate-early gene expression

Glazenburg¹,

Peeters²,

Pol³

et al. 1995

J Virol

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To investigate how altered control of expression of the essential immediate-early (IE) gene of pseudorabies virus influences virus replication and virulence, we replaced the IE promoter with the tissue-specific promoters of the bovine cytokeratin IV gene (CKIV), the bovine cytokeratin VIb gene (CKVIb), or the inducible promoter of Drosophila heat shock gene HSP70. We compared expression of the IE gene of the wild-type virus and recombinant viruses in different cell types and at different temperatures and found that IE expression had become cell type or temperature dependent. When a recombinant virus was titrated on nonpermissive cells or was titrated at nonpermissive temperatures in vitro, the plating efficiency was reduced by more than 99%. Mice were inoculated subcutaneously (s.c.), intraperitoneally (i.p.), or intranasally (i.n.) with a dose equal to 100 times the 50% lethal dose of the wild-type virus. After inoculation with temperature-sensitive recombinant N-HSP, two (s.c.), two (i.p.), and four (i.n.) of five mice died. However, at this dose, recombinant N-CKIV, which contains a promoter specific for stratified epithelial tissue of the tongue mucosa, was not lethal when inoculated s.c. or i.p. but killed four mice when inoculated i.n. Recombinant N-CKVIb, which contains a promoter specific for the suprabasal layers of the epidermis, was not lethal after inoculation by any of the three routes. In explant cultures of nasal mucosa of pigs, replication of N-CKIV and N-CKVIb was not markedly reduced in the epithelium. However, in contrast to results obtained with wild-type virus, infection of the stroma was not observed. We conclude that the replicative ability and virulence of pseudorabies virus can be influenced by altering control of expression of the IE gene.

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Adeno-associated Virus Based Vectors As Antivirals

Wong¹,

Chatterjee

1996

Adeno-Associated Virus (AAV) Vectors in Gene Therapy

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Controlling Herpes Simplex Virus Infections: is Intracellular Immunization the Way of the Future?

Cited by 5 publications

References 91 publications

Inhibition of Replication of Reactivated Human Immunodeficiency Virus Type 1 (HIV-1) in Latently Infected U1 Cells Transduced with an HIV-1 Long Terminal Repeat-Driven PKR cDNA Construct

Inhibition of Replication of Reactivated Human Immunodeficiency Virus Type 1 (HIV-1) in Latently Infected U1 Cells Transduced with an HIV-1 Long Terminal Repeat-Driven PKR cDNA Construct

Construction and properties of pseudorabies virus recombinants with altered control of immediate-early gene expression

Adeno-associated Virus Based Vectors As Antivirals

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