Biomedical subjects

J Rajcáni

Publications and source records attributed to J Rajcáni.

At least 19 recordsLinked to original sources

PubMed2006

Developments in herpes simplex virus vaccines: old problems and new challenges.

Vaccination has remained the best method for preventing virus spread. The herpes simplex virus (HSV) candidate vaccines tested till now were mostly purified subunit vaccines and/or recombinant envelope glycoproteins (such as gB and gD). In many experiments performed in mice, guinea pigs and rabbits, clear-cut protection against acute virus challenge was demonstrated along with the reduction of the extent of latency, when established in the immunized host. The immunotherapeutic effect of herpes vaccines seems less convincing. However, introduction of new adjuvants, which shift the cytokine production of helper T-cells toward stimulation of cytotoxic T-cells (TH1 type cytokine response), reveals a promising development. Mathematical analysis proved that overall prophylactic vaccination of seronegative women, even when eliciting 40-60 % antibody response only, would reduce the frequency of genital herpes within the vaccinated population. Even when partially effective, immunotherapeutic vaccination might represent a suitable alternative of chronic chemotherapy in recurrent labial and genital herpes.

Adjuvants, Immunologic↗

PubMed2004

Leukemia-like syndrome in Balb/c mice infected with the lymphotropic gamma herpesvirus MHV-Sumava: an analogy to EBV infection.

Based on our previous observation that primary infection with the murine gamma herpesvirus (MHV) isolate Sumava (MHV-SU) undergoes a lymphoproliferative phase resembling to Epstein-Barr virus (EBV) induced infectious mononucleosis (IM), we evaluated white blood cell (WBC) counts at late stages following MHV-SU infection. In consequence of intranasal inoculation with MHV-SU a leukemia-like syndrome in Balb/c mice developed. The syndrome in question was accompanied with significant splenomegaly; in the peripheral blood leukocytosis (from 8 x 10(4) to 5 x 10(5) leukocytes/microl) and a high percentage of atypical lymphocytes (60-80%) was found. Presented results are bringing further evidence for lymphoproliferative effect of MHV and point at analogic course of MHV-SU and EBV infections.

Animals↗

PubMed2004

Expression of herpes simplex virus 1 glycoprotein D in prokaryotic and eukaryotic cells.

Recombinant plasmids encoding either the full-length glycoprotein D (FLgD) or truncated gDs were constructed. The recombinant plasmids were expressed in Escherichia coli and BHK-21 cells. The strongest expression was obtained with the recombinant plasmid encoding a truncated gD which corresponded to the gD ectodomain. The cells transformed with this plasmid showed good exponential growth ensuring satisfactory yields of the expressed polypeptide in the form of the fusion protein. The fusion protein was biotinylated and efficiently purified. The shortest truncated gD, which contained the main continuous antigenic locus VII binding neutralization antibody and additional continuous antibody binding epitopes, still reacted with specific antibody as proven by immunoblot analysis. In addition, a shuttle vector for expression of FLgD in mammalian cells was constructed. This vector-transfected BHK-21 cells expressed gD for 40 days during 9 consecutive passages. The expression of gD began on day 2 and culminated at day 9 post transfection (p.t.).

Animals↗

PubMed2003

Gamma herpesviruses: pathogenesis of infection and cell signaling.

Altered cell signaling is the molecular basis for cell proliferation occurring in association with several gamma herpesvirus infections. Three gamma herpesviruses, namely EBV/HHV-4, KSHV/HHV-8 and the MHV-68 (and/or MHV-72) and their unusual cell-pirated gene products are discussed in this respect. The EBV, KSHV as well as the MHV DNA may persist lifelong in an episomal form in the host carrier cells (mainly in lymphocytes but also in macrophages, in non-hornifying squamous epithelium and/or in blood vessel endothelial cells). Under conditions of extremely limited transcription, the EBV-infected cells express EBNA1 (EB nuclear antigen 1), the KSHV infected cells express LANA1 (latent nuclear antigen 1), while the MHV DNA carrier cells express the latency-associated protein M2. With the full set of latency-associated proteins expressed, EBV carrier cells synthesize additional EBNAs and at least one LMP (latent membrane protein 1). The latent KSHV carrier cells, in addition to LANA1, may express a viral cyclin, a viral Fas-DD-like ICE inhibitor protein (vFLIP) and a virus-specific transformation protein called kaposin (K12). In MHV latency with a wide expression of latency-associated proteins, the carrier cells express a LANA analogue (ORF73), the M3 protein, the K3/IE (immediate early) proteins and M11/bcl-2 homologue proteins. During the period of limited gene expression, the latency-associated proteins serve mainly for the maintenance of the latent episomal DNA (a typical example is EBNA1). In contrast, during latency with a broader spectrum gene expression, the virus-encoded products activate transcription of otherwise silenced cellular genes, which leads to the synthesis of enzymes capable of promoting not only viral but also cellular DNA replication. Thus, the latency-associated proteins block apoptosis and drive host cells towards division and immortalization. Proliferation of hemopoetic cells, which had become gamma herpesvirus DNA carriers, can be initiated and strongly enhanced in the presence of inflammatory cytokines and by virus-encoded analogues of interleukins, chemokines and IFN regulator proteins. At early stages of tumor formation, many proliferating hemopoetic and/or endothelium cells, which had became transcriptionally active under the influence of chemokines and cytokines, may not yet be infected. In contrast, at later stages of oncogenesis, the virus-encoded proteins, inducing false signaling and activating the proliferation pathways, bring the previously infected cells into full transformation burst.

Animals↗

PubMed2003

Molecular mechanisms of virus spread and virion components as tools of virulence. A review.

Despite of differences in replication strategy among virus families, some basic principles have remained similar. Analogous mechanisms govern virus entry into cells and the use of enzymes which direct the replication of the virus genome. The function of many cell surface receptors (such as glycosoaminoglycans, glycoproteins, proteins) which interact with viral capsid proteins or envelope glycoproteins has recently been elucidated. The list of cellular receptors (Table I) is still far from being final. The capsid components, similarly as the envelope glycoproteins, may form specific pocket like sites, which interact with the cell surface receptors. Neutralizing antibodies usually react with antigenic domains adjacent to the receptor binding site(s) and hamper the close contact inevitable for virion attachment. In the case of more complex viruses, such as herpes simplex virus, different viral glycoproteins interact with several cellular receptors. At progressed phase of adsorption the virions are engulfed into endocytic vesicles and the virion fusion domain(s) become(s) activated. The outer capsid components of reoviruses which participate in adsorption and fusion may get activated already in the lumen of digestive tract, i.e. before their engulfment by resorptive epithelium cells. Activation of the hydrophobic fusion domain(s) is a further important step allowing to pass through the lipid bilayer when penetrating the cell membrane in order to reach the cytosol. Activation of the virion fusion domain is accomplished by a conformation change, which occurs at acid pH (influenza virus hemagglutinin, sigma 1 protein of the reovirus particle) and/or after protease treatment. The herpes simplex virus fusion factors (gD and gH) undergo conformation changes by a pH-independent mechanism triggered due to interaction with the cell surface receptor(s) and mediated by mutual interactions with the viral envelope glycoproteins. The virion capsid or envelope components participating in the entry and membrane fusion are not the only tools of virulence. The correct function of virus coded proteins, which participate in replication of the viral genome, and/or in the supply of necessary nucleotides, may be very essential. In the case of enteroviruses, which RNA interacts with ribosomes directly, the correct configuration of the non-coding viral RNA sequence is crucial for initiation of translation occurring in the absence of the classical "cap" structure.

Animals↗

PubMed2003

Detection of immediate early protein ICP27/IE63 and thymidine kinase in the course of reactivation of latent herpes simplex virus 1 infection.

We followed the kinetics of reactivation of latent Herpes simplex virus 1 (HSV-1) infection established in rabbits by corneal route. The corresponding trigeminal ganglia (TG) were cultured and the culture medium was examined at daily intervals for release of infectious virus. Sections from the cultured TG fragments were stained with antisera against non-structural proteins such as the immediate early (IE) protein ICP27 and the early (E) proteins thymidine kinase (TK), the large subunit of ribonucleotide reductase (RR1), the ori-binding protein OBP and with a human serum obtained from volunteers immunized with an experimental subunit HSV-1 envelope (env) vaccine containing late structural proteins gB1, gC1, gD1 and gG1 (env antiserum). By indirect immunofluorescence (IF) test, ICP27 was detected in a few neurons from day 1 post explantation (p.e.), while TK was observed in neurons from day 2 p.e. Fluorescence with the human env antiserum was seen at day 3 p.e. The RR1 and OBP antisera stained productively infected Vero cells from 3 and 4 hrs post inoculation (p.i.), respectively. However, these sera showed no IF in cultured ganglion fragments at any interval examined. Our results showed the same cascade of HSV-1 IE and E protein expression during productive infection and reactivation in vitro.

Animals↗

PubMed2001

A simple procedure for expression and purification of selected non-structural (alpha and beta) herpes simplex virus 1 (HSV-1) proteins.

The expression and isolation of herpes simplex virus 1 (HSV-1) immediate early (alpha) IE63 (ICP27) and of the early (beta) thymidine kinase (Tk) polypeptides in Escherichia coli JM 109 cells transformed with the PinPoint Xa-1 (Promega) plasmid construct carrying either the HSV-1 UL54 or UL23 genes are described. The resulting biotinylated fusion protein(s) could be easily induced and were purified in appropriate amounts by means of a monomeric avidin-conjugated resin (SoftLink Soft Release Avidin Resin, Promega) provided that: (1) the exponential growth of the selected transformed cells was monitored carefully; (2) the post-induction harvest interval was properly chosen; and (3) the period for adsorption to the avidin resin suitably adjusted. The isolated protein(s), although partially digested in the case of the IE63 polypeptide, were suitable antigen(s) for immunization of various animal species. Co-purification of trace amounts of endogenous biotinylated protein(s) produced in E. coli was eliminated by shortening the duration of adsorption to the avidin resin.

Electrophoresis, Polyacrylamide Gel↗

PubMed2001

The UL9 ori-binding protein of herpes simplex virus 1: its expression and localization in vero cells.

The ori-binding protein (OBP), an early protein which is encoded by the herpes simples virus 1 (HSV-1) UL9 gene and initiates the replication of viral DNA, was expressed in Escherichia coli, purified on an avidin resin and used for preparation of a mouse antiserum to OBP (OBP antiserum). Expression and localization of OBP in HSV-1-infected Vero cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and indirect immunofluorescence test. RT-PCR revealed the presence of abundant UL9 transcripts from 3 to 12 hrs post infection (p.i). Traces of UL9 mRNA were detected already at 1.5 hr p.i. The OBP antiserum detected clumps of irregularly shaped structures in the nuclei of infected Vero cells first at 4 hrs p.i. These nuclear structures peaked at 5-6 hrs p.i. and later on (at 8-12 hrs p.i.) they changed into fine granules filling the whole nucleus.

Animals↗

PubMed2000

Early expression of herpes simplex virus (HSV) proteins and reactivation of latent infection.

During the last decade, new data accumulated describing the early events during herpes simplex virus 1 (HSV-1) replication occurring before capsid formation and virion envelopment. The HSV virion carries its own specific transcription initiation factor (alpha-TIF), which functions together with other components of the cellular transcriptase complex to mediate virus-specific immediate early (IE) transcription. The virus-coded IE proteins are the transactivator and regulatory elements modulating early transcription and subsequent translation of nonstructural virus-coded proteins needed mainly for viral DNA synthesis and for the supply of corresponding nucleoside components. They also cooperate at the late transcription and translation of the virion (capsid, tegument and envelope) proteins. In addition, the transactivator IE proteins down-regulate their own transcription, while others facilitate viral mRNA processing or interfere with the presentation of newly synthesized virus antigens. Establishment of latency is closely related to the transcription of a separate category of transcripts, termed latency-associated (LAT). Formation of LATs occurs mainly in nondividing neurons which are metabolically less active and express lower levels of cellular transcription factors (nonpermissive cells). Expression of the stable non-spliced (2 kb), and especially of stable spliced (1.5 and 1.45 kb) LATs is a prerequisite for HSV reactivation. Different HSV genomes (from various HSV strains) do not undergo IE transcription at the same rate. Restricted IE transcription and the absence of viral DNA synthesis favors LAT formation and persistence of the silenced genome. Uneven levels of LAT expression and differences in the metabolic state of carrier neurons influence the reactivation competence. Under artificial or natural activation conditions, sufficient amounts of IE transactivator proteins and proteins promoting nucleoside metabolism are synthesized even in the absence of the viral alpha-TIF facilitating reactivation.

Animals↗

PubMed2000

Herpes simplex virus 1 (HSV-1) strain HSZP glycoprotein B gene: comparison of mutations among strains differing in virulence.

The nonpathogenic HSZP strain of HSV-1 induces large polykaryocytes due to a syn3 mutation (His for Arg at residue 858) in the C-terminal endodomain of glycoprotein B (gB) (40). We determined the nucleotide (nt) sequence of the UL27 gene specifying the gB polypeptide of HSZP (gBHSZP) and found 3 mutations in its ectodomain at aminoacids (aa) 59, 79 and 108. The ANGpath virus, which also has a syn3 mutation in the C-terminal endodomain of gB (Val for Ala at residue 855) is pathogenic for adult mice (39), but can be made nonpathogenic by replacing the gBANGpath gene by the corresponding gBKOS sequence (21). The gBANGpath had three ectodomain mutations (at aa 62, 77 and 285), while gBKOS had at least four ectomain mutations (aa 59, 79, 313, and 553). Two mutations (aa 59 and 79) in the latter, located in the variable antigenic site IV/D1 were common for gBKOS and gBHSZP. These together with the gBANGpath mutations at aa 62 and 77 create a cluster of 4 mutations in diverse region of the N-terminal part of gB (between aa 59-79), in which the gBs of pathogenic ANGpath and 17 viruses differ from the gBs of nonpathogenic HSZP and KOS viruses. The lower pathogenicity of KOS as related to gBKOS, is furthermore associated with the change of Ser to Thr at aa 313 (locus III/D2). The possibility is discussed that mutations in both above mentioned antigenic loci could result in higher immunogenicity of the corresponding antigenic epitopes, which, in turn, would contribute to the decreased virulence of HSZP and KOS viruses.

Amino Acid Substitution↗

PubMed2000

Characterization of glycoprotein C of HSZP strain of herpes simplex virus 1.

Sequences of UL44 genes of strains HSZP, KOS and 17 of herpes simplex virus 1 (HSV-1) were determined and the amino acid sequences of corresponding glycoproteins (gC) were deduced. In comparison with the 17 strain, the HSZP strain showed specific changes in 3 nucleotides and in 2 amino acids (aa 139 and 147, both from Arg to Trp) in the antigenic locus LII. The change at aa 147 was situated within the GAG-binding epitope. In a similar comparison, KOS strain had changes in 3 nucleotides and 3 amino acids (aa 3, 14, and 300). The UL44 genes of HSZP and KOS strains were expressed in insect Sf-21 cells by means of the baculovirus (Bac-to-Bac) expression system. As shown by immunoblot analysis, both the recombinant baculoviruses (B1-HSZP and B6-KOS) expressed a glycosylated gC, the M(r) of which (116 K) was lower than that of gC synthesized in Vero cells (129 K) infected with strains HSZP or KOS. In addition, smaller gC-specific proteins (of apparent M(r) of 50-58 K and 98 K) corresponding to a non-glycosylated precursor polypeptide and/or incomplete forms of the partially glycosylated gC were found. When Balb/c mice were immunized with Sf-21 cells expressing gC, the recombinant gC-HSZP represented a more efficient immunogen possibly due to its stronger expression in these cells. The corresponding gC-HSZP antiserum reacted in enzyme-linked immunosorbent assay (ELISA) equally well with HSZP and KOS virion antigens and neutralized HSZP strain at a low titer. Both gC-HSZP and gC-KOS antisera detected the homologous as well as the heterologous gC antigens in Vero cells regardless whether infected with strains HSZP, KOS or 17, revealing the presence of gC from 6 to 16 hrs post infection (p.i.) in the cytoplasm, on the nuclear membrane and at the cell surface.

Animals↗

PubMed1999

Characterization of strain HSZP of herpes simplex virus type 1 (HSV1).

The genetic background of HSZP virus, an HSV1 strain with extensive passage history, was analyzed by parallel comparative sequencing of four relevant genes (UL27/gB, UL41/vhs, UL44/gC and UL53/gK) of HSZP and additional three selected viruses [strains ANGpath, strains KOS(a) and KOS(b) and the prototype strain 17]. Mutation at position 858 (His for Arg) in gB of HSZP was found to be responsible for giant cell formation (syn3gB mutation) similarly as the 855 mutation (Val for Ala) in the gB of ANGpath. No syn1gK mutations were detected in the UL53 gene either of HSZP or of ANGpath viruses. The reduced virulence of HSZP for adult mice after peripheral inoculation, similarly as that of KOS virus, seems to be related (at least in part) to numerous mutations in the gB ectodomain. Of these, two mutations located in the antigenic domain IV were the same in gBHSZP as well as in gBKOS (at amino acids 59 and 79), at least two (amino acids 313 and 553) were specific for gBKOS, while one mutation (Ser for Ala at position 108) was specific for gBHSZP. The abolished shutoff function of the HSZP virus was related to at least four out of six specific mutations seen in the vhs polypeptide (vhsHSZP) encoded by the UL41 gene, of which three (amino acids 374, 386, 392) were clustered in the semiconservative box A of vhsHSZP (the truncation of which abrogates the inhibition provided by this protein) and one mutation (at amino acid 18) was situated in the highly conservative locus I of vhsHSZP. In addition, the two vhsKOS specific mutations (amino acids 19 and 317) not found in vhsHSZP, enhanced the early host shutoff function of the vhsKOS protein. Finally, gCHSZP had two specific mutations (amino acids 137 and 147) located in the antigenic domain II of gC, which is responsible for binding of HSV1 virions to the glycosoaminoglycan (GAG) receptor. When expressed in Sf21 cells using the recombinant baculovirus system (Bac-to-Bac), gCHSZP and gCKOS showed no essential antigenic differences.

Amino Acid Sequence↗

PubMed1999

Interference of the low-pH inactivated herpes simplex virus type 1 (HSV-1) strain HSZP with the early shutoff function of superinfecting HSV-1 strain KOS.

In former studies, we described that the HSZP strain of herpes simplex virus type 1 (HSV-1) was defective with respect to the early shutoff of host protein synthesis but was effective at interfering with the early shutoff function of the HSV-1 strain KOS, even when heat-inactivated or neutralized by antibody. However, the HSZP strain failed to interfere when inactivated with zinc ions or purified from cells treated with 2-deoxy-D-glucose. In this study, we provide evidence that the ability of the purified low-pH inactivated (citrate buffer, pH 3.0) and gel-filtered (Sephadex G-25) HSZP virions to adsorb host cells was not significantly affected. However, their ability to induce interference with the early shutoff function of the superinfecting HSV-1 strain KOS was restricted. In comparison with native virus, up to eight times more low-pH inactivated HSZP virions were needed to interfere with the shutoff by strain KOS. The interference was not due to exclusion of strain KOS by HSZP at the level of adsorption and/or penetration. The restriction was partially overcome by treatment of the cells with polyethylene glycol after adsorption of the low-pH inactivated HSZP virions. This observation indicates that the direct fusion of the virion envelope of low-pH inactivated HSZP with the plasma cell membrane was predominantly hampered.

Animals↗

PubMed1999

Glycoprotein K of herpes simplex virus: a transmembrane protein encoded by the UL53 gene which regulates membrane fusion.

Glycoprotein K (gK) encoded by the UL53 gene is the ninth out of eleven HSV glycoproteins (gps). The precursor gK (pgK) is a transmembrane protein with four hydrophobic domains, which consists of 338 amino acids. The UL53 gene has two initiation codons: the upper overlaps with the UL52 ORF, while the lower is located 55 codons downstream and specifies a truncated precursor of the gK polypeptide. The UL53 gene and the upstream located UL52 gene have a common polyadenylation signal downstream from the UL53 stop codon so that the UL53 mRNA is completely nested within the UL52 transcript. The syn1 mutations in several KOSsyn mutants and in the MPsyn virus, which had been fine mapped to DNA coordinates 0.735-0.740, were later on located to the UL53 gene, especially to its portion which specifies the first 120 amino acids (aa) from the N-terminus (most frequently residue 40) and to a less precisely defined locus between aa 301-310 (close to the C-terminus). Point mutations in the N-terminal ectodomain of gK, which are related to syn formation, impair the putative ability of this region to down-regulate membrane fusion. The two N-glycosylated mannose core oligosaccharides are attached to the Asn residues of the gK polypeptide at positions 48 and 58, respectively. In infected cells, gK is localized mainly in the nuclear and endoplasmic reticulum (ER) membranes. It is not clear, whether gK becomes incorporated into the envelope of mature HSV particles. Studies with the insertion/deletion gK mutants showed the importance of gK for capsid envelopment, for the transportation and egress or virions from infected cells. It seems that gK has an essential role in virion egress, even though this glycoprotein acts in accord with gH and with another membrane protein encoded by the UL20 gene.

Alphaherpesvirinae↗

PubMed1999

Increased neoplasm development due to immunosuppressive treatment with FK-506 in BALB/C mice persistently infected with the mouse herpesvirus (MHV-72).

BALB/c mice were infected with the lymphotropic mouse gammaherpesvirus (MHV-72). At late (7-12 months) post-infection intervals the latent virus was detected in the cells of lymphatic system (peripheral blood, lymphocytes and macrophages, thymocytes, lymph nodes, bone marrow, and peritoneal macrophages,) and in the spleen, lungs, liver, and kidney by cocultivation as well as by explantation. The MHV-72 infected mice, in which latency had been established, were treated with the immunosuppressive (IS) drug FK-506 (2 mg/kg/mouse for 30 days). This treatment increased the probability of virus reactivation by over two-fold. During the post-treatment observation period of 19 months, the incidence of lymphomas and the development of MHV-related lymphoproliferative and hemoblastic disorders raised to nearly five-fold in the drug treated mice as compared to untreated animals.

Animals↗

PubMed1998

Syn strains HSZP and ANGpath [correction of ANG] of herpes simplex virus type 1 do not contain mutations in the regions of UL53 gene relevant to syncytium formation.

Parallel sequencing of UL53 gene of four strains of herpes simplex virus type 1 (HSV-1), two of which (HSZP and ANGpath) were of the syn phenotype while another two (KOS and 17) were of the non-syn phenotype, showed in three strains amino acid mutations unrelated to the already described syn1 glycoprotein K (gK) mutations (Dolter et al., 1994). The only mutations which altered encoded amino acids were found in strains HSZP (Gln to Arg at position 198) and ANGpath (Val to Ile at position 137). Both mutations were localised outside of the two mutation clusters suspected for affecting syncytium formation. In addition, a CG/GC variation was found at positions 245-246 and 669-670. These compressions affected three codons altering amino acids (aa) 82 (Cys or Ser), 223 (Me or Ile) and 224 (Leu or Val), respectively.

Animals↗

PubMed1998

The role of herpes simplex virus glycoproteins in the virus replication cycle.

At least nine of the eleven herpes simplex virus (HSV) glycoproteins so far known have been widely characterised as regards their role in the virus replication cycle. During early virus-to-cell adsorption ("adsorption"), glycoprotein C (gC) interacts with the glycosoaminoglycan (GAG) heparan sulphate (HS), located on the cell membrane surface. This interaction is labile until other glycoproteins such as B and D (gB and gD) begin to participate in the entry process. gB also harbours a site for interaction with GAGs, while gD provides a stabile attachment to cellular receptors ("receptors") such as the herpesvirus entry mediator (HVEM). Late adsorption is associated with a conformation change of gD occurring after the receptor binding, a step followed by interaction of gD with the gH/gL heterodimer (complex). Fusion domains of the gH/gL complex and gB enable the pH-independent virus-into-cell penetration ("penetration"). The gE/gI complex and gM interact with the receptors at cell junctions in order to facilitate cell-to-cell spread of the virus along the basolateral surface of polarised cells and/or a similar intercellular spread in nonpolarised cells by avoiding virion release, gK, the only so far known HSV-coded glycoprotein which is not incorporated into virions, plays an essential role in the virus capsid envelopment at the nuclear membrane and in the virion transport to the cell surface. Unusually large polykaryocytes arise due to mutations in syn (syncytium) loci of the viral genome, which were mapped to UL53 (syn1) and UL27 (syn3) genes coding for gK and gB, respectively, while the genes UL20 and UL24 (both syn5) code for nonglycosylated cell membrane-associated proteins ("membrane proteins"). The products of nonmutated syn genes either downregulate the fusion of plasma membranes of infected cells ("membrane fusion") or protect them from undesirable fusion events.

Adsorption↗

PubMed1997

Herpes simplex virus type 1 (HSV-1) strain HSZP host shutoff gene: nucleotide sequence and comparison with HSV-1 strains differing in early shutoff of host protein synthesis.

The UL41 gene of the HSZP strain of herpes simplex virus type 1 (HSV-1) defective with respect to the early shutoff of host protein synthesis was sequenced and compared with the corresponding HSV-1 strain KOS and 17 gene sequences. In comparison with strain 17, nine mutations (base changes) were HSZP specific, five KOS specific and four were common for both strains. Nine mutations caused codon changes. Three of these mapped to the nonconserved regions and the others to the conserved regions of the functional map of UL41 gene. One KOS specific mutation mapped to the region responsible for the binding of the virion host shutoff (vhs) protein to the alpha-transinducing factor (VP16). The possible relationship between mutations and host shutoff function is discussed. The nucleotide sequence data of the UL41 gene of HSZP and KOS have been submitted to the Genbank nucleotide database and have been assigned the accession numbers Z72337 and Z72338.

Amino Acid Sequence↗