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A L Epstein

Publications and source records attributed to A L Epstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

A new chemically modified chimeric TNT-3 monoclonal antibody directed against DNA for the radioimmunotherapy of solid tumors.

In the last several years, our laboratory has developed a new approach to the radioimmunotherapy of solid tumors, designated Tumor Necrosis Treatment (TNT), that exploits the presence of degenerating and necrotic cells within tumors by utilizing MAbs directed against universal, intracellular antigens. The first TNT MAb developed by our laboratory, designated TNT-1, was directed against nucleosomal determinants consisting of histone H1 and DNA. Since absolute tumor accretion of MAb is a critical determinant of antitumor efficacy in radioimmunotherapy, we sought to identify new antinuclear antibodies that displayed high tumor localization properties. In the present study, we describe a murine antinuclear antibody, TNT-3, which demonstrates 3-fold higher tumor uptake than TNT-1. Because of this characteristic, a chimeric derivative designated chTNT-3 was developed and evaluated for antigen binding and tumor targeting. ELISA studies using a series of nuclear antigens confirmed that TNT-3 is directed against single-stranded DNA and does not cross react with TNT-1. Immunohistology reveals predominantly nuclear staining reactivity in human tissues and tumors. Since it was shown by our laboratory that charge modification can significantly improve the pharmacokinetic performance of monoclonal antibodies, chTNT-3 was chemically modified with biotin to generate an improved therapeutic reagent designated chTNT-3/B. Comparative studies with unmodified MAb demonstrated that biotinylation significantly shortened its clearance time in mice and produced lower normal tissue levels, while maintaining an equal amount of uptake in tumor xenografts for up to 10 days. These in vivo characteristics suggest that chTNT-3/B is an improved TNT reagent for the radioimmunotherapy of solid tumors.

Animals↗
PubMed1998

Improving monoclonal antibody pharmacokinetics via chemical modification.

The aim of radioimmunotherapy in treating solid tumors is to target tumor sites while sparing normal tissues. This can best be achieved by using a monoclonal antibody (MAb) with high tumor uptake and rapid clearance. Because MAbs are basic, positively charged proteins, and mammalian cells are negatively charged, the electrostatic interactions between the two can create higher levels of background binding resulting in low tumor to normal organ ratios. To overcome this effect, investigators have attempted to improve MAb clearance by using various methods such as secondary agents as well as chemical and charge modifications of the MAb itself. The use of a second agent to remove the MAb involves using a biotinylated MAb followed by treatments with a molecule like avidin. Charge modification can be accomplished by conjugating a chemical moiety with a positive, negative or neutral charge to residues exposed on the surface of MAbs. Experimental results demonstrate that the lowering of the isoelectric point by this method correlates with a decreased clearance time and improved tumor targeting. Altering the pharmacokinetic characteristics of intact MAbs with charge modification can improve their clearance times to rates similar to those of MAb fragments. Several groups have reported on the effects of chemical modification using molecules such as dextran, PEG, lactose and biotin. Some of these modified MAbs retain the antigen binding specificity of the parent molecule and have improved clearance characteristics from blood and other organs. Hence, these methods can be used to improve both the diagnostic and therapeutic potential of MAbs by improving the signal to noise ratio and the absolute tumor accretion of MAb, respectively.

Animals↗
PubMed1997

Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo.

Lym-2 is a murine monoclonal antibody (MoAb) directed towards a human class II molecule variant reactive with both normal and neoplastic human B lymphocytes. Previous studies have shown that signals transmitted by class II molecules that stimulate normal lymphocytes can be inhibitory for B-cell lymphoma growth by signaling activation-induced cell death. Therefore, we sought to evaluate the effects of nonconjugated murine Lym-2 and a human-mouse chimeric Lym-2 (chCLL-1; with murine variable regions and human constant regions) MoAb on the growth of various human lymphomas by using both in vitro and in vivo assays. Cell lines derived from Burkitt's lymphomas, diffuse large cell B-cell lymphomas, anaplastic large-cell lymphomas, and Epstein-Barr virus-induced B-cell lymphomas were incubated with Lym-2 or chCLL-1 in vitro, and effects on proliferation were determined by [3H]-thymidine incorporation. The effects of Lym-2 in vitro were also compared with those of Lym-1, which is a similar MoAb that has been evaluated clinically. After immobilization, which enhances crosslinking of the MoAbs, both Lym-2 and chCLL-1 were capable of directly inhibiting the growth of various lymphoma lines in vitro. These human lymphomas were then transferred into mice with severe combined immunodeficiency to evaluate the efficacy of these MoAbs in vivo. Treatment with either murine Lym-2 or the chimeric chCLL-1 were significantly effective in improving the survival of tumor-bearing mice. These results indicate that stimulation by nonconjugated chCLL-1 may offer a biological approach to the treatment of various human lymphomas.

Animals↗
PubMed1997

Chimeric CLL-1 antibody fusion proteins containing granulocyte-macrophage colony-stimulating factor or interleukin-2 with specificity for B-cell malignancies exhibit enhanced effector functions while retaining tumor targeting properties.

Although monoclonal antibody (MoAb) therapy of the human malignant lymphomas has shown success in clinical trials, its full potential for the treatment of hematologic malignancies has yet to be realized. To expand the clinical potential of a promising human-mouse chimeric antihuman B-cell MoAb (chCLL-1) constructed using the variable domains cloned from the murine Lym-2 (muLym-2) hybridoma, fusion proteins containing granulocyte-macrophage colony-stimulating factor (GM-CSF) (chCLL-1/GM-CSF) or interleukin (IL)-2 (chCLL-1/IL-2) were generated and evaluated for in vitro cytotoxicity and in vivo tumor targeting. The glutamine synthetase gene amplification system was employed for high level expression of the recombinant fusion proteins. Antigenic specificity was confirmed by a competition radioimmunoassay against ARH-77 human myeloma cells. The activity of chCLL-1/GM-CSF was established by a colony formation assay, and the bioactivity of chCLL-1/IL-2 was confirmed by supporting the growth of an IL-2-dependent T-cell line. Antibody-dependent cellular cytotoxicity against ARH-77 target cells demonstrated that both fusion proteins mediate enhanced tumor cell lysis by human mononuclear cells. Finally, biodistribution and imaging studies in nude mice bearing ARH-77 xenografts indicated that the fusion proteins specifically target the tumors. These in vitro and in vivo data suggest that chCLL-1/GM-CSF and chCLL-1/IL-2 have potential as immunotherapeutic reagents for the treatment of B-cell malignancies.

Animals↗
PubMed1997

Cell type-specific expression in brain cell cultures from a short human cytomegalovirus major immediate early promoter depends on whether it is inserted into herpesvirus or adenovirus vectors.

Expression from a short human cytomegalovirus (HCMV) major immediate early (IE) promoter-enhancer was tested in three different virus vectors: recombinant adenovirus (Ad), recombinant herpes simplex virus type 1 (HSV-1) and HSV-1-derived amplicon vectors. The HCMV major IE promoter-enhancer within a replication-deficient recombinant Ad vector was shown to produce cell-specific expression in rat nervous system cell cultures. Recombinant Ad entered all cell types examined but the HCMV major IE promoter was silent in primary cultures of neocortical neurons and Schwann cells, although it drove transgene expression in astrocytes and fibroblasts. Moreover, in neurons and Schwann cells, expression from the HCMV major IE promoter-enhancer in the replication-deficient Ad vector was activated by superinfection with HSV-1, replication-competent Ad and HCMV. The HCMV major IE promoter-enhancer was active in neurons when inserted into HSV-1 recombinant vectors. Further experiments with HSV-1-derived amplicons strongly suggested that an IE protein was responsible for the activation of HCMV major IE-induced expression in neurons. This demonstrates that the activity of the HCMV major IE promoter-enhancer element can depend on the expression of other genes encoded in the virus vector backbone within which it is inserted, and that it can function in a neuronal cell type-specific manner when inserted into a replication-deficient Ad vector.

Adenoviridae↗
PubMed1997

Equimolar generation of the four possible arrangements of adjacent L components in herpes simplex virus type 1 replicative intermediates.

Herpes simplex virus type 1 (HSV-1) replication generates high-molecular-weight intermediates containing branched DNA and concatemers carrying adjacent genomes with inverted L components. We have studied replicative intermediates generated by (i) wild-type HSV-1; (ii) 5dl1.2, an ICP27 null mutant which fails to synthesize normal amounts of DNA and late proteins; (iii) RBMu3, a mutant containing a deletion in the inverted repeats which fails to generate genomic isomers; and (iv) amplicon plasmids and vectors which contain no inverted sequences. Replication intermediates were analyzed by pulsed-field gel electrophoresis, after restriction enzyme digestion of infected-cell DNA, followed by blot hybridization. DNA fragments were statistically quantified after phosphorimaging. We observed that (i) the four possible configurations of L components of two adjacent genomes in the concatemers are present at equimolar amounts at any time during virus replication, (ii) ICP27 is not required for inversions or for branched DNA to occur, and (iii) replication intermediates of both RBMu3 mutant and amplicon plasmids or vectors do contain branched structures, although the concatemers they generate contain no inversions. These data indicate that inversions are generated by a mechanism intrinsically linked to virus DNA replication, most likely homologous recombination between inverted repeats. Branched structures are detected in all replicating molecules, including those that do not invert, suggesting that they are constitutively linked to virus DNA synthesis. Our results are consistent with the notion that the four HSV-1 genomic isomers are generated by alternative cleavage frames of replication concatemers containing equimolar amounts of L-component inversions.

Animals↗
PubMed1997

Defective herpes simplex virus type 1 vectors harboring gag, pol, and env genes can be used to rescue defective retrovirus vectors.

A retroviral packaging transcription unit was constructed in which the Moloney murine leukemia virus (MoMLV) gag-pol and env genes are expressed under the control of herpesvirus regulatory sequences. This transcription unit, lacking long terminal repeats, primer binding sites, and most of the retrovirus packaging signal but retaining both retroviral donor and acceptor splice sites, was cloned into a herpes simplex virus type 1 (HSV-1) amplicon plasmid, and amplicon vectors (the gag-pol-env [GPE] vectors) were generated by using a defective HSV-1 vector as helper virus. The GPE vector population was used to infect human TE671 cells (ATCC CRL 8805), harboring a lacZ provirus (TE-lac2 cells), and supernatants of infected cells were collected and filtered at different times after infection. These supernatants were found to contain infectious ecotropic lacZ retroviral particles, as shown both by reverse transcription-PCR and by their ability to transduce a beta-galactosidase activity to murine NIH 3T3 cells but not to human TE671 cells. The titer of retroviral vectors released by GPE vector-infected TE-lac2 cells increased with the dose of infectious amplicon particles. Retrovirus vector production was inhibited by superinfection with helper virus, indicating that helper virus coinfection negatively interfered with retrovirus production. Induction of retrovirus vectors by GPE vectors was neutralized by anti-HSV-1 but not by anti-MoMLV antiserum, while transduction of beta-galactosidase activity to NIH 3T3 cells by supernatants of GPE vector-infected TE-lac2 cells was neutralized by anti-MoMLV antiserum. These results demonstrate that HSV-1 GPE amplicon vectors can rescue defective lacZ retrovirus vectors and suggest that they could be used as a sort of launching ramp to fire defective retrovirus vectors from within virtually any in vitro or in vivo cell type containing defective retroviral vectors.

Defective Viruses↗
PubMed1997

Exploration of novel strategies to enhance monoclonal antibodies targeting.

This paper highlights the major obstacles and prospects of antibody targeting for the radioimaging and therapy of human malignant lymphomas and more challenging solid tumors. To improve the therapeutic potential of monoclonal antibodies, we have focused our attention on the development of new and successful methods to augment antibody uptake in the tumor. These approaches include the use of radiolabeled streptavidin to target biotinylated monoclonal antibodies already bound to tumor, pretreatment with vasoactive immunoconjugates, and the use of chemically modified antibodies. Because of the promising preclinical data obtained with these three newer approaches, plans are underway to test them in the clinic. More generally, these approaches are applicable to the use of other monoclonal antibody/tumor systems for the diagnosis and therapy of human cancers and related diseases.

Antibodies, Monoclonal↗
PubMed1996

A chimeric Lym-1/interleukin 2 fusion protein for increasing tumor vascular permeability and enhancing antibody uptake.

A murine antihuman B-cell monoclonal antibody, Lym-1, has shown considerable promise for the treatment of human malignant lymphomas. To enhance its clinical potential, a genetically engineered fusion protein consisting of a chimeric Lym-1 (chLym-1) and interleukin 2 (IL-2) was tested for mediating cytotoxicity, increasing vasopermeability, and enhancing antibody uptake in human malignant lymphomas. The chLym-1/IL-2 fusion protein, which was expressed initially in a baculovirus system and more recently in the glutamine synthetase gene amplification system, was shown to be processed and assembled into a normal immunoglobulin monomer with two IL-2 molecules per antibody. It was found to be equivalent to the chLym-1 antibody in antigen-binding specificity and relative affinity. In addition, it maintains IL-2 cytokine activity as demonstrated by support of T-cell proliferation. Moreover, in antibody-dependent cellular cytotoxicity assays against Raji target cells, chLym-1/IL-2 had approximately 2-fold and 4-fold higher cytotoxicity than chLym-1 and murine Lym-1, respectively. Used as a pretreatment, chLym-1/IL-2 enhances the uptake of chLym-1 at the tumor site by altering the permeability of tumor vessels producing tumor:normal organ ratios of 420:1 for blood and 1708:1 for muscle at 3 days. The in vitro and in vivo activities of chLym-1/IL-2, therefore, suggest that this genetically engineered antibody fusion protein may represent a new immunotherapeutic reagent for the treatment of human malignant lymphomas.

Animals↗
PubMed1996

Increased transcomplementation properties of plasmids carrying HSV-1 origin of replication and packaging signals.

This report describes a very simple method that facilitates the analysis of the functional activity of essential genes of herpes simplex virus type 1 (HSV-1) in cell culture. The method, which depends on the use of complementing plasmids containing a virus origin of replication (ori s) and a packaging signal (amplicon plasmids), was tested for its ability to detect complementation of the defective HSV-1 Cgal delta 42 virus, a UL42 null mutant, by amplicon plasmids carrying either wild-type (pA-UL42) or mutated alleles (pA-delta UL42) of the HSV-1 UL42 gene. In nonpermissive Vero cells transfected with amplicon plasmid pA-UL42 and superinfected with the defective Cgal delta 42 virus, both the plasmid and the helper genomes were amplified and packaged, giving rise to a self-complementing amplicon/helper virus population able to disseminate and to form lytic plaques in cell culture. These plaques were due to complementation and not to recombination between the defective virus and the amplicon plasmid as confirmed by Southern blot analysis of individual plaques. No complementation was observed by superinfection of cells transfected with the noncomplementing pA-delta UL42 amplicon plasmid. Instead, small foci were observed in cells transfected with plasmids which express wild-type UL42 but were unable to amplify or to become packaged, and the few true lytic plaques that were observed in these systems resulted from the spread of competent recombinant viruses. Results presented in this work indicate that (i) self-complementation between a defective virus and an amplicon plasmid provides a strong and very sensitive method to assess function activity of an HSV-1 essential gene in a one-step experiment and (ii) oris-carrying plasmids could be instrumental in the production and selection of recombinant HSV-1 vectors.

Animals↗
PubMed1996

Improved tumor localization and radioimaging with chemically modified monoclonal antibodies.

A method for the chemical modification of monoclonal antibodies using the heterobifunctional crosslinker succinimidyl 3-(2-pyridyldithio)propionate (SPDP), has been developed which dramatically alters the physiochemical properties of antibody reagents. For these studies, three murine monoclonal antibodies, B72.3, Lym-1, and TNT-1 were used to demonstrate the effects of chemical modification on clearance and biodistribution in tumor-bearing nude mice. In vitro, all three antibodies, modified to the same degree with SPDP, showed equal immunoreactivities and lower non-specific binding. Modified antibodies also were found to have lower isoelectric points compared to unmodified controls. In vivo, modified antibodies unexpectedly were found to have 2-6 times faster clearance in tumor-bearing nude mice similar to rates obtained with their F(ab')2 fragments. Paired-label in vivo biodistribution and external imaging experiments with intact antibodies and F(ab')2 fragments demonstrated that chemically modified antibodies gave 1.5-3 fold higher tumor uptake and retained less activity in normal organs thus markedly increasing the tumor to normal organ ratios. Because of these results, chemically modified antibodies produced clearer images at earlier time points by external scintigraphy. As "stealth" molecules, chemically modified monoclonal antibodies appear to have significantly improved uptake in tumors and faster clearance times compared to native molecules. These results suggest that alteration of the physicochemical properties of monoclonal antibodies may generate improved reagents for in vivo use.

Animals↗
PubMed1995

Identification of a monoclonal antibody, TV-1, directed against the basement membrane of tumor vessels, and its use to enhance the delivery of macromolecules to tumors after conjugation with interleukin 2.

mAbs reactive with epitopes expressed on tumor vessels were evaluated as universal delivery agents of peptides with vasoactive properties to enhance the uptake of macromolecules in tumors. Unlike other reported approaches to target tumor vessels, a mAb designated TV-1 targets a basement membrane antigen that is found in all tissues but that is accessible only in tumor vessels, making it an alternative vehicle for the delivery of biologically active peptides to tumors. A panel of 30 monoclonal and polyclonal antibodies was screened by immunohistochemistry on sections of human tumors, normal vascular endothelium, and connective tissues. Five antibodies were chosen for in vivo evaluation, including two antifibronectin antibodies (TV-1, HFN 7.1), one anti-basic fibroblast growth factor antibody (anti-BFGF), and two antibodies reactive with a mesenchymal cell antigen (TP-1, TP-3). Three nude mouse tumor models characterized by varying degrees of vascularization (low to high) were used. After chemical conjugation to interleukin 2 (IL-2), these antibodies were used to pretreat tumor-bearing nude mice 3 h before injection with a radiolabeled mAb directed to the transplanted tumors. Pretreatment with TV-1/IL-2 or HFN 7.1/IL-2 produced a 3-fold higher tumor uptake of radiolabel compared to control mice pretreated with mAb alone. The other three vasoactive immunoconjugates failed to show significant increases in these tumor models. When TV-1/IL-2 was compared with the specific vasoconjugate (Lym-1/IL-2) as a pretreatment in the Raji lymphoma model, which has low vascularization, TV-1/IL-2 yielded approximately 60% of the tumor uptake seen with Lym-1/IL-2. In comparison, pretreatment with TV-1/IL-2 in the LS174T colon carcinoma model, which has high vascularization, yielded approximately the same tumor uptake seen with the B72.3/IL-2 vasoconjugate, which directly targets the tumor cells. These studies demonstrate that a mAb directed against fibronectin in the endothelial subcellular matrix can be used to deliver vasoactive agents to tumors.

Animals↗
PubMed1995

Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress.

The promyelocytic leukemia protein fused to the retinoic acid receptor alpha in t(15;17) acute promyelocytic leukemia, the primary biliary cirrhosis autoantigen, Sp100, as well as the incompletely characterized protein NDP55, are co-localized in specific immunohistochemically defined nuclear domains (ND10), which are potential equivalents of ultrastructurally defined nuclear bodies. We investigated whether the distribution of these proteins depends on environmental conditions and whether ND10 correlate with nuclear bodies. Certain nuclear bodies and ND10 react in a similar way and share antigens. Interferon exposure doubled the number of ND10 and increased the frequency of nuclear bodies, whereas herpes simplex virus infection or heat shock modify both. Redistribution of ND10-associated proteins to hundreds of small sites throughout the chromatin was inducible by stress in the form of heat shock and exposure to Cd++ ions. The change of distribution was rapid and independent of protein synthesis, and thus not part of the classical heat shock response. The very rapid redistribution of these proteins after heat shock, together with the development of ND10 upon interferon activation, raises the possibility that ND10 represent storage sites of certain matrix proteins readily accessible throughout the chromatin in response to stress or other effectors that induce global nuclear changes.

Antigens, Nuclear↗
PubMed1995

Simultaneous detection of amplicon and HSV-1 helper encoded proteins reveals that neurons and astrocytoma cells do express amplicon-borne transgenes in the absence of synthesis of virus immediate early proteins.

HSV-1 amplicon vectors were used to express either a cytoplasmic (beta-galactosidase) or a membrane targeted protein (TIMP-Thy1) in primary neuronal cultures, and a human astrocytoma cell line. Whereas some cells became infected by vector particles alone others were simultaneously infected by both vector and helper particles. Our results show that IEHCMV and HSV-1 IE3 promoters are able to direct transgene expression in these cells in the absence of synthesis of helper virus transacting proteins, and stress the need of monitoring expression from both partners of an amplicon population, in order to differentiate transgene expression in cells singly infected with amplicon particles, from those infected by both amplicon and helper particles.

Astrocytes↗
PubMed1995

Herpes simplex virus type 1 replication and recombination.

Herpesviruses are a very interesting model for studying DNA replication in eukaryotic systems since they encode most of the proteins required for this process. These include a protein that specifically binds to the virus origin of DNA synthesis, a single-stranded DNA binding protein, an heterotrimeric helicase-primase and an heterodimeric DNA polymerase holoenzyme. Although the virus genome contains three origins of DNA synthesis, replication proceeds through the generation of high molecular mass concatemeric replicative intermediates reminiscent of rolling circles. In addition, herpesviruses are highly recombinogenic and are useful models to study homologous recombination. Homologous recombination and replication of the virus genome appear to be tightly coupled and interrelated processes.

Animals↗
PubMed1995

Potentiation of antiproliferative effects of monoclonal antibody Lym-1 and immunoconjugate Lym-1-gelonin on human Burkitt's lymphoma cells with gamma-interferon and tumor necrosis factor.

A type I ribosome inactivating protein, gelonin, was linked to Lym-1, a murine monoclonal antibody reactive with a polymorphic determinant of class II HLA-DR histocompatibility leukocyte antigen (HLA) on human lymphoma cells, via a disulfide linkage using the heterobifunctional cross-linking agent, N-succinimidyl-3-(2-pyridyldithio) propionate. This immunotoxin was purified from unreacted gelonin and unconjugated Lym-1 by fast protein liquid chromatography using sephacryl S-300 gel filtration and blue sepharose affinity gradient separation. Binding of Lym-1-gelonin immunoconjugate to human Raji Burkitt's lymphoma cells was demonstrated by indirect immunofluorescence using flow cytometry. Lym-1-gelonin was very active in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium salt and sulforhodamine B in vitro cytotoxicity assays against the Raji lymphoma cell line and confirmed the fact that monoclonal antibody Lym-1 internalizes into human lymphoma cells. A weaker cytostatic antiproliferative effect was also noted for unconjugated Lym-1. gamma-interferon augmented the antiproliferative effects of Lym-1-gelonin conjugate and unconjugated Lym-1, by having a direct cytotoxic effect on the Raji cells. Tumor necrosis factor-alpha also enhanced the antiproliferative effect of unconjugated Lym-1, but did not significantly augment the cytotoxic activity of the Lym-1-gelonin conjugate. These results suggest that anti-HLA class II monoclonal antibodies may be useful in constructing immunotoxins for the treatment of human lymphomas and leukemias expressing HLA class II antigens, and that unconjugated anti-HLA class II monoclonal antibodies may be therapeutically useful in conjunction with recombinant cytokines, especially gamma-interferon.

Animals↗
PubMed1995

Cloning, sequencing, and functional characterization of the two subunits of the pseudorabies virus DNA polymerase holoenzyme: evidence for specificity of interaction.

The pseudorabies virus (PRV) genes encoding the two subunits of the DNA polymerase were located on the genome by hybridization to their herpes simplex virus type 1 (HSV-1) homologs, pol and UL42, and subsequently were sequenced. Like the HSV-1 homologs, in vitro translation products of the PRV gene encoding the catalytic subunit (pol) possessed activity in the absence of the Pol accessory protein (PAP). However, the PRV PAP stimulated the activity of Pol fourfold in the presence of 150 mM KCl, using an activated calf thymus DNA template. The stimulation of Pol activity by PAP under high-salt conditions and the inhibition of Pol activity by PAP when assayed in low salt (0 mM KCl) together were used to determine the specificity with which PAP interacted with Pol. Despite functional similarity, HSV-1 UL42 and PRV PAP could neither stimulate the noncognate Pols at high salt nor inhibit them at low salt. Furthermore, a PRV Pol mutant lacking the 30 C-terminal amino acids retained basal Pol activity but could be neither stimulated nor inhibited by the PRV PAP. Sequence comparisons of the Pol proteins of the alphaherpesviruses reveal a conserved domain in the C terminus which terminates immediately before the last 41 residues of both PRV and HSV-1 proteins. These results indicate that the ability and specificity for interaction of the PRV Pol with PAP most likely resides predominantly in the extreme Pol C terminus.

Amino Acid Sequence↗