SEARCH · Search PubMed

Results for “lytic replication”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1995

Brain irradiation and antioedematous dexamethasone treatment--risk factors for herpes simplex encephalitis?

Herpes simplex encephalitis (HSE) could result from the reactivation of an endogenous latent herpes simplex virus (HSV) in sensory ganglia or in brain parenchyma. Virus replication and a new lytic virus cycle may be triggered by a wide variety of factors. One of these might be irradiation as suggested by experimental evidence obtained in mouse trigeminal ganglia. Here we report the occurrence of HSE in a 52 years old woman two months after brain irradiation (40 Gray in 20 fractions) and dexamethasone administration for a metastatic brain tumor. HSE has already been observed in a clinical context very similar to that reported here, suggesting that brain irradiation together with corticoid therapy may, in some rare patients, favour the occurrence of HSV reactivation and HSE.

Antineoplastic Agents, Hormonal↗

PubMed1986

Orientation and sequence analysis of right ends and target sites of bacteriophage mu and D108 insertions in the plasmid pSC101.

We have isolated four independent insertions of the entire 37-kb D108cts 10 genome in the low-copy-number plasmid pSC101 in vivo. They were all formed by replicative transposition during the D108 lytic cycle. The orientation of these four insertions was found to be the same, with the left ends facing towards pSC101 replication, and the right end facing in the direction of all pSC101 transcription, as was previously found for a Mucts62 insertion in pSC101, pMC321. The exact sites of insertion of two of the D108 prophages, as well as the Mu prophage, have been determined by sequence analysis. All three insertions caused a 5-bp duplication of pSC101 sequences at the target site, as has been found for insertions formed by conservative integration upon lysogeny. Moreover, we have determined the nucleotide sequence of the first 75 bp of the right end of D108 and, though this end is interchangeable with the right end of Mu as a substrate for either phage's transposition functions, there are a number of nucleotide differences between them.

Base Sequence↗

PubMed1995

Halophage HF2: genome organization and replication strategy.

Halophage HF2 is a lytic, broad-host-range bacteriophage of the extremely halophilic domain Archaea. It has a 79.7-kb double-stranded DNA genome which is linear, contains no modified nucleotides, and is not susceptible to cleavage by many type II restriction endonucleases. This insensitivity is attributed to selection against palindromic restriction sites, a commonly observed feature of broad-host-range phages. Interestingly, enzymes that did cut the genome recognized AT-rich sites, and five such enzymes, DraI, AseI, HpaI, HindIII, and SspI, were used to construct a physical map of the genome. Southern hybridization experiments used to order fragments on the map indicated homologies between the phage termini, and subsequent sequence analysis showed that HF2 possessed 306-bp direct terminal repeats. The presence of such repeats suggested replication through concatameric intermediates, and this was confirmed by analysis of the state of the phage genome in infected cells. This is a replication strategy adopted by many well-studied bacterial phages, for example T3 and T7. Other similarities between the terminal repeats of T3 or T7 and HF2 include a putative nick site at the repeat border and a series of short imperfect repeats. These observations suggest a long evolutionary history for concatamer-based strategies of phage replication, possibly predating the divergence of Archaea/Eucarya and Bacteria, or alternatively, indicate possible lateral transfer of phage genes or modules between the domains Archaea and Bacteria.

Bacteriophages↗

PubMed2005

Functional characterization of the repA replication gene of linear plasmid prophage N15.

The prophage of coliphage N15 is not integrated into the chromosome, but exists as a linear plasmid molecule with covalently closed ends. The only phage gene required for replication of circular N15 miniplasmids is repA (gene 37). Here we show that RepA-driven replication of the N15-based circular and linear miniplasmids is independent of host DnaB helicase protein, but requires the host DnaG primase. Replication of phage N15 DNA during lytic growth following infection does not depend on either DnaG or DnaB, but DnaG is required for lytic development after induction of the N15 lysogen. Finally, protein sequence analysis and replication data using different mutant strains suggest that RepA protein combines helicase and primase functions.

Adenosine Triphosphatases↗

PubMed1984

Stoichiometric use of the transposase of bacteriophage Mu.

The transposase of bacteriophage Mu (gene A protein) mediates the coupled replication and integration processes that constitute transposition during the lytic cycle. Our previous results showed that the activity of the A protein is unstable, as its continued synthesis is required to maintain Mu DNA replication throughout the lytic cycle. We present here the results of experiments in which the A protein is used stoichiometrically and must be synthesized de novo for each round of Mu DNA replication. Induction of a Mu lysogen in the absence of DNA replication allows accumulation of potential for a single round of Mu DNA replication. Once achieved, this potential is stable even in the absence of further protein synthesis. Release of inhibition of DNA replication leads to a single semi-conservative replicative transposition event, followed by later rounds only if additional synthesis of the A protein is allowed.

Bacteriophage mu↗

PubMed1997

Novel alleles of the Escherichia coli dnaA gene.

The Escherichia coli dnaA gene is required for replication of the bacterial chromosome. To identify residues critical for its replication activity, a method to select novel mutations was developed that relied on lytic growth of lambda from an inserted pSC101 replication origin. Replication from the lambda origin was inhibited by lysogen-encoded cI repressor. Replication from the pSC101 origin that resulted in lytic growth was dependent on active DnaA protein encoded by a plasmid in a host strain lacking the chromosomal dnaA gene. With this approach, a large collection of missense, nonsense, and a few internal deletion mutations were obtained. Nucleotide sequence analysis of the missense mutations indicated that 28 of 50 were unique. Of these, one was identical to the dnaA205 allele whereas the remainder are novel. These missense mutations were clustered into three regions, suggesting three functional domains of DnaA protein required for its replication activity. Many of the missense mutations mapping to the C-terminal 61 residues were inactive for replication from the pSC101 origin. These are defective in DNA binding. Mutations that mapped elsewhere were temperature-sensitive.

Alleles↗

PubMed2025

Characterization of the Kaposi's sarcoma-associated herpesvirus terminase complex component ORF29.

Kaposi's sarcoma-associated herpesvirus (KSHV) belongs to the Gammaherpesvirinae subfamily. During the lytic phase of herpesviruses, viral capsids form in the host cell nucleus, and the replicated viral genome is packaged into these capsids. The herpesviral genome is replicated as a precursor head-to-tail concatemer consisting of tandemly repeated genomic units, each flanked by terminal repeats (TRs). The herpesvirus terminase complex packages a single genomic unit into a capsid by cleaving the TRs in the precursor genome. Although the terminase complexes of alpha- and beta-herpesviruses are well characterized, the KSHV terminase complex is poorly understood. KSHV ORF7, ORF67.5, and ORF29 are thought to be components of this complex. We previously reported that KSHV deficient in either ORF7 or ORF67.5 formed immature, soccer ball-like capsids and failed to cleave the TRs, resulting in decreased virion production. Moreover, ORF7 interacted with both ORF29 and ORF67.5; however, ORF29 and ORF67.5 did not interact with each other. Thus, although ORF7 and ORF67.5 are important for KSHV terminase function, the function of ORF29 remains largely unknown. In this study, we constructed an ORF29-deficient KSHV and analyzed its virological properties. ORF29 was found to be essential for virion production and TR cleavage. Numerous immature, soccer ball-like capsids were observed in cells harboring ORF29-deficient KSHV. The N-terminal region of ORF29 was important for its interaction with ORF7, although the full-length ORF29 was required for effective assembly of the KSHV terminase complex. Furthermore, ORF29 preferentially interacted with itself rather than with ORF7. Thus, our data show that ORF29 functions as a fundamental component of the terminase complex.IMPORTANCEBecause the role of ORF29 in the Kaposi's sarcoma-associated herpesvirus (KSHV) terminase complex remains unknown, we constructed ORF29-deficient KSHV. Our results demonstrated that ORF29 functions as a component of the KSHV terminase and is essential for mature capsid formation, terminal repeat (TR) cleavage, and terminase complex assembly. Moreover, ORF29 strongly interacted with itself. In herpes simplex virus 1 (HSV-1), the terminase complex (comprising UL15, UL28, and UL33) forms a trimer, and six such trimers assemble into a hexameric ring. The HSV-1 genome passes through this ring and undergoes TR cleavage and genome packaging into a capsid. The self-interaction of ORF29 may be involved in the multimerization of the terminase complex or in the formation of the KSHV terminase ring.

Herpesvirus 8, Human↗

PubMed2005

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 RTA reactivates murine gammaherpesvirus 68 from latency.

Murine gammaherpesvirus 68 (MHV-68), Kaposi's sarcoma-associated herpesvirus (HHV-8), and Epstein-Barr virus (EBV) are all members of the gammaherpesvirus family, characterized by their ability to establish latency in lymphocytes. The RTA protein, conserved in all gammaherpesviruses, is known to play a critical role in reactivation from latency. Here we report that HHV-8 RTA, not EBV RTA, was able to induce MHV-68 lytic viral proteins and DNA replication and processing and produce viable MHV-68 virions from latently infected cells at levels similar to those for MHV-68 RTA. HHV-8 RTA was also able to activate two MHV-68 lytic promoters, whereas EBV RTA was not. In order to define the domains of RTA responsible for their functional differences in viral promoter activation and initiation of the MHV-68 lytic cycle, chimeric RTA proteins were constructed by exchanging the N-terminal and C-terminal domains of the RTA proteins. Our data suggest that the species specificity of MHV-68 RTA resides in the N-terminal DNA binding domain.

Animals↗

PubMed2002

Identification of an HLA A*0201-restricted CD8(+) T-cell epitope for the glycoprotein B homolog of human herpesvirus 8.

Human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpesvirus)-specific cytotoxic T-lymphocyte (CTL) and interferon-gamma (IFN-gamma) responses to proteins produced during the lytic cycle of HHV-8 replication are mediated by HLA class I-restricted, CD8(+) T cells. We have characterized the fine specificity of the CD8(+) T-cell response to 25 peptides derived from 5 HHV-8 lytic cycle proteins based on a prediction model for HLA A*0201 binding motifs. One of the 25 HLA A*0201 peptides derived from the glycoprotein B (gB) homolog of Epstein-Barr virus (gB(492-500); LMWYELSKI; single-letter amino acid codes) bound to HLA A*0201 and stimulated IFN-gamma responses in CD8(+) T cells from HHV-8(+), HLA A*0201 persons, but not HHV-8-seronegative or non-HLA A*0201 persons. The peptide also induced IFN-gamma and CTL reactivity to naturally processed gB protein. The peptide was a major immunogenic epitope of HHV-8 as indicated by induction of IFN-gamma responses in peripheral blood mononuclear cells from 5 of 5 HHV-8 seropositive, HLA A*0201 persons when gB(492-500) was presented by autologous dendritic cells. T-cell reactivity to gB(492-500) was not related to detectable HHV-8 DNA in the blood. These data show that CD8(+) T cells recognize an HLA A*0201-restricted epitope for HHV-8 lytic cycle protein gB, particularly when presented by dendritic cells. This epitope may be important in control of HHV-8 infection by CD8(+) T cells.

Amino Acid Sequence↗

PubMed2004

Epstein-Barr virus (EBV) SM protein induces and recruits cellular Sp110b to stabilize mRNAs and enhance EBV lytic gene expression.

Promyelocytic leukemia protein (PML) nuclear bodies or nuclear domain 10s (ND10s) are multiprotein nuclear structures implicated in transcriptional and posttranscriptional gene regulation that are disrupted during replication of many DNA viruses. Interferon increases the size and number of PML nuclear bodies and stimulates transcription of several genes encoding PML nuclear body proteins. Moreover, some PML nuclear body proteins colocalize at sites of viral DNA synthesis and transcription. In this study, the relationship between lytic Epstein-Barr virus (EBV) replication and Sp110b, a PML nuclear body protein, was investigated. Sp110b is shown to physically and functionally interact with the EBV protein SM. SM is expressed early in the EBV replicative cycle and posttranscriptionally increases the level of target EBV lytic transcripts. SM bound to Sp110b via two distinct sites in Sp110b in an RNA-independent manner. SM also specifically induced expression of Sp110b during lytic EBV replication and in several cell types. Exogenous expression of Sp110b synergistically enhanced SM-mediated accumulation of intronless and lytic viral transcripts. This synergistic effect was shown to be promoter independent, posttranscriptional, and the result of increased stabilization of target transcripts. Finally, inhibiting Sp110b expression decreased accumulation of an SM-responsive lytic EBV transcript in EBV-infected cells. These findings imply that SM induces Sp110b expression, binds to Sp110b, and utilizes the recruited Sp110b protein to increase the stability of lytic EBV transcripts, indicating that Sp110b is a component of the cellular machinery that EBV utilizes to enhance lytic EBV replication.

B-Lymphocytes↗

PubMed1984

Synchronization of bacteriophage Mu DNA replicative transposition: analysis of the first round after induction.

The lytic cycle of bacteriophage Mu includes a large number of coupled DNA replication and integration events, each of which is equivalent in several respects to the process of transposition of genetic elements. To aid us in studying the process of Mu DNA replicative transposition, we developed a technique for synchronizing the first round of replication following induction of a lysogen. Synchronization was achieved by inducing a lysogen in the absence of DNA replication for a time sufficient to develop the potential for Mu DNA replication in all cells in the population; upon release of the inhibition of replication, a synchronized round of Mu DNA replication was observed. Development of the potential for Mu DNA replication in the entire population took approximately 12 min. Protein synthesis was required for development of the potential, but the requirement for protein synthesis was satisfied by approximately 9 min suggesting that other, as yet unspecified, reactions occupied the last 3 min. Replication proceeded predominantly from the left end of the prophage, though a significant amount of initiation from the right end was observed. The usefulness of the technique for studying the mechanism of replicative transposition and the end products of a single round of replication are discussed.

Bacteriophage mu↗

PubMed1996

Epstein-Barr virus single-stranded DNA-binding protein: purification, characterization, and action on DNA synthesis by the viral DNA polymerase.

Epstein-Barr virus (EBV) BALF2 gene product is one of the essential components in the lytic phase of the EBV DNA replication. The BALF2 protein was purified to near homogeneity from the nuclear extract of B95-8 cells with virus productive cycle induced by chemical agents. SDS-polyacrylamide gel electrophoresis showed the presence of a single polypeptide with a molecular weight of 130 K, which was identified as BALF2 protein by Western immunoblot analysis. On Superose 6 HR 10/30 gel filtration the BALF2 protein eluted at a position corresponding to an apparent molecular mass of approximately 128 K, indicating that the BALF2 protein behaves as a monomer in solution. The purified BALF2 protein bound to single-stranded DNA preferentially over double-stranded DNA or single-stranded RNA. Replication of singly primed M13 single-stranded DNA by the EBV DNA polymerase complex in the absence of the BALF2 protein exhibited a highly processive mode of replication and generated full length products in addition to some bands of pausing sites. Although the addition of the BALF2 protein did not affect the replication rate, the average chain length of the replication products was slightly increased with eliminating bands of pausing sites. Similar effects were observed with the reconstituted polymerase complex composed of the BALF5 and BMRF1 Pol subunits. On the other hand, in the absence of the BALF2 protein, the BALF5 Pol catalytic subunit alone extended the primer slightly and paused at specific sites on M13 ssDNA template where stable secondary structure is predicted. However, addition of the BALF2 protein, in contrast to the case of herpes simplex virus ICP8 which does not affect the overall distribution of length of the replication products synthesized by the HSV Pol catalytic subunit (Gottlieb et al., 1990, J. Virol. 64, 5976-5987), stimulated DNA synthesis and yielded a distribution of replication products with long lengths in addition to full length products. Although the BALF2 protein behaved as if it converts a low processive enzyme of the EBV Pol catalytic subunit to a highly processive form like the BMRF1 Pol accessory subunit, challenger DNA experiments revealed that the EBV Pol catalytic subunit is transferred to challenger DNA even in the presence of the BALF2 protein. It is therefore likely that the EBV BALF2 protein functions to melt out the regions of secondary structure on the single-stranded DNA template, thereby reducing and eliminating pausing of the EBV DNA polymerase at specific sites. These properties indicate that the EBV BALF2 protein acts as a single-stranded DNA-binding protein during lytic phase of EBV DNA replication.

Animals↗

PubMed1986

Free and viral chromosome-bound simian virus 40 T antigen: changes in reactivity of specific antigenic determinants during lytic infection.

Simian virus 40 (SV40) large T antigen (TAg), both free and bound to mature 70S and replicating 90S SV40 chromosomes, was prepared from lytically infected cells. The relative reactivity of the different TAg-containing fractions toward 10 monoclonal antibodies directed against three different regions in SV40 TAg and toward an antibody against the p53 protein was measured. The results for free TAg indicated that all of the determinants in both the amino-terminal (0.65 to 0.62 map units) and carboxy-terminal (0.28 to 0.17 map units) regions were highly reactive, whereas all five determinants located between 0.43 and 0.28 map units in the midregion of TAg were poorly reactive. For TAg bound to replicating chromosomes, all but one of the antibodies specific for TAg were highly reactive. Thus, antigenic sites in the middle of TAg, the region important for nucleotide binding and ATP hydrolysis (an activity required for viral DNA replication), were more accessible in TAg-replicating DNA complexes. As replicating molecules matured into 70S chromosomes, three or more determinants at different locations in TAg bound to chromatin became two- to fivefold less reactive, indicating other changes in TAg structure. Overall, at least nine different antigenic determinants in the TAg molecule were identified. Anti-p53 was reactive with about 10% of the free TAg and the same amount of SV40 chromosomes of all ages, suggesting that p53-TAg complexes are not preferentially associated with either replicating or mature viral chromosomes. When the reactivity of both mature and replicating labeled SV40 chromosomes with polyclonal tumor anti-T was measured as a function of time after purification, TAg bound to mature chromosomes appeared to dissociate about fourfold faster than that bound to replicating chromosomes. The relative amount of TAg in various subcellular fractions was measured by an enzyme-linked immunosorbent assay. Approximately 1.3% of the total TAg was estimated to be associated with SV40 chromosomes in infected cells. Based on the relative amounts of TAg and viral DNA in the 70S and 90S fractions, replicating chromosome-TAg complexes were estimated to bind 4.8 times more TAg per DNA molecule, on the average, than mature chromosome-TAg complexes. Together, these results are consistent with major differences in TAg structure when free and associated with replicating and nonreplicating SV40 chromosomes.

Animals↗

PubMed2005

KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2.

Kaposi sarcoma (KS) remains the most common AIDS-associated malignancy worldwide. In sub-Saharan Africa especially, this aggressive endothelial-cell tumor is a cause of widespread morbidity and mortality. Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is now known to be an etiologic force behind KS and primary-effusion lymphoma (PEL). Over time, KSHV has pirated many human genes whose products regulate angiogenesis, inflammation, and the cell cycle. One of these, the KSHV vGPCR, is a lytic product that is a constitutively active homolog of the IL-8 receptor. Although it is considered a viral oncogene and causes KS-like lesions in mice, vGPCR expression results in cell-cycle arrest of KSHV-infected PEL cells. In the present study, we show that this arrest is mediated by p21 in a p53-independent manner; the resulting Cdk2 inhibition decreases the efficiency of chemical induction of KSHV lytic transcripts ORF 50 and 26. Importantly, Cdk2 activity is also essential for replication in other human herpesviruses. The ability of vGPCR to delay or abort KSHV replication may explain how despite being a lytic product, this potent signaling molecule has a vital role in tumor formation via its induction of various KS-associated cytokines.

Cell Cycle↗

PubMed1990

Analysis by in situ hybridization and autoradiography of sites of replication and storage of single- and double-stranded adenovirus type 5 DNA in lytically infected HeLa cells.

The distribution in the different compartments of infected nuclei of double-stranded (ds) and single-stranded (ss) adenovirus type 5 (Ad5) DNA and of the sites of viral DNA replication were examined on thin sections of Low-icryl-embedded material. The DNA is visualized with a biotinylated viral probe and immunogold labeling of biotin, and its replication is monitored by high-resolution autoradiography after short pulses with tritiated thymidine. The first detectable sites of viral DNA, named early replicative sites, contained all the ss and ds viral DNA and viral replicative activity. At a later stage of nuclear transformation, they gave rise to two new structures. The compact fibrillar ssDNA accumulation sites enlarged greatly and became transformed functionally to become a transient site of accumulation of large numbers of ss replicative intermediates. Double-stranded viral DNA and its replicative activity shifted primarily into immediately surrounding fibrillogranular peripheral replicative zones. Ad5 DNA replication continues in the ssDNA accumulation sites but it is intermittent, whereas in the peripheral replicative zones it is continuous. Still later in infection, a single, large, centrally located mass of dense fibrils, the viral genome storage site, developed in each nucleus which proved to be the main site of storage of nonreplicating, nonencapsidated, ds viral genomes. We discuss the possible distribution of the various viral DNA replicative intermediates among these virus-induced intranuclear structures.

Adenoviruses, Human↗

PubMedDate not supplied

Functional analysis of Kaposi's sarcoma-associated herpesvirus RTA in an RTA-depressed cell line.

OBJECTIVE: The viral transcriptional activator encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50 (RTA) is expressed in the immediate-early phase of reactivation. We isolated an RTA-depressed cell line, BLS50-4, by subcloning from the KSHV-infected cell line, BCBL-1. RESULTS: In addition to RTA, induction of some lytic gene expressions was also remarkably reduced in BLS50-4 cells, but that of the K8.1 and ORF65 gene expressions was not. Both the replication of the KSHV genome and the release of KSHV DNA into the medium were greatly reduced. Transfection of RTA into BLS50-4 cells restored the expression of K9 (vIRF) and ORF59, but not K8.1. CONCLUSIONS: Thus, we showed that expression of late genes was not directly controlled by RTA, unlike the other groups concluded. We also showed that, by isolating the RTA-depressed cell line, the RTA protein had a critical role in viral DNA replication and the expression of several lytic genes.

Cell Line↗

PubMed2005

Esterified whey proteins can protect Lactococcus lactis against bacteriophage infection. Comparison with the effect of native basic proteins and L-polylysines.

Inhibitory action of basic esterified milk whey proteins [methylated (Met) or ethylated (Et) beta-lactoglobulin (BLG) and alpha-lactalbumin (ALA)], basic native proteins (chicken egg white lysozyme and calf thymus histone), and basic protein-like substances (L-polylysines) against the activity and replication of lactococcal bacteriophages (bIL66, bIL67, and bIL170) was tested. Chemical interactions of these proteins with phage DNA were determined as well as their protective effect on the growth of a laboratory plasmid-cured Lactococcus lactis subjected to an infection by the bacteriophages. All the proteins studied showed inhibitory activity against the three bacteriophages as tested by marked reduction of their lytic activities and decreasing the replication of studied phages. Histone and Met-BLG were more active toward bIL66 and bIL67, respectively, while both proteins were highly and equally active toward bIL170. Lysozyme showed lower antiviral activity. Antiviral activity of Et-BLG was a little bit lower than that observed in the case of the Met derivative. Esterified ALA also showed considerable but slightly lower antiviral activity as compared to other proteins. L-polylysines also showed an antiviral effect against the three bacteriophages studied, their influence being highly dependent on their molecular size. The best effective size of L-polylysines was in the range 15-70 kDa. Replication of bIL67 was inhibited by the presence of esterified ALA or BLG and native basic proteins. Complete inhibition of replication of bIL67 occurred when using polylysines with molecular masses in the ranges 4-15, 15-30, and 30-70 kDa, while protein-like substrates with lower molecular masses had only a slight effect. The presence of histone and Met-BLG at a concentration of 0.13 mg/mL in the incubation medium protected L. lactis against lysis when it was subjected to an infection by bIL67 (10(5) pfu/mL). The same action was achieved by l-polylysine (15-30 kDa) used at a concentration of 0.03 mg/mL in the incubation medium.

Bacteriophages↗

PubMed1993

Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene.

Little is known about virus-host cell interactions that regulate the lytic potential of viruses during productive replication. Sindbis virus (SV), a single-stranded positive-sense RNA virus in the alphavirus genus (family Togaviridae), results in lytic infection in most vertebrate cell lines, but persistent productive infection in post-mitotic neurons. The cellular oncogene bcl-2, which encodes an inner mitochondrial membrane protein of M(r) 26,000 (ref. 2), blocks programmed cell death (apoptosis) in neurons. We therefore investigated whether SV infection induces programmed cell death in non-neuronal cells, and if so, whether virus-induced programmed cell death can be blocked by transfection with bcl-2. We demonstrate that SV infection of baby hamster kidney (BHK-2), mouse neuroblastoma (N18), and rat prostatic adenocarcinoma (AT-3) cells results in programmed cell death, whereas SV infection of bcl-2-transfected AT-3 cells results in long-term persistent productive infection. Thus cellular bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced programmed cell death.

Adenocarcinoma↗