Journal of Organic Chemistry (March 2002) 67:1536

Serine and Threonine Beta-Lactones:[?] A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors

Mass spectrometry and HMQC NMR studies using (13)C-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the beta-position of the oxetanone ring. Although the N-Cbz-serine beta lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the beta-lactone ring for binding.'

Journal of Biological Chemistry (Jan. 2002)(e-pub ahead of print)

HBV pX Interacts with XAP-8 PHD Finger Protein to Coactivate Transcription

HBV gene expression is mainly regulated at the transcription initiation level. The viral X protein (pX) is a transcriptional coactivator/mediator targeting TFIIB for the recruitment of RNA Polymerase II. Here we report a novel pX nuclear target designated XAP-8 (pX associated protein 8). XAP-8 is a novel cellular nuclear protein containing a PHD (Plant Homology Domain) finger, a domain shared by many proteins that play roles in chromatin remodeling, transcription coactivation and oncogenesis. pX physically interacts with XAP-8 in vitro and in vivo via the XAP-8 region containing the PHD finger. At the functional level XAP-8 increases HBV transcription in a pX dependent manner, suggesting a role for this interaction in the virus life cycle. Interestingly, XAP-8 collaborates with pX in coactivating the transcriptional activator NF-kappaB. Coactivation of NF-kappaB was also observed in TNF-alpha-treated cells suggesting that pX-XAP-8 functional collaboration localized downstream to the NF-kappaB nuclear import. Collectively our data suggest that pX recruits and potentiates a novel putative transcription coactivator to regulate NF-kappaB. The implication of pX-XAP-8 interaction in the development of hepatocellular carcinoma is discussed.'

Journal of Medical Virology (April 2002):468

Lack of Susceptibility of Chacma Baboons(Papio ursinus orientalis) to Hepatitis C Virus Infection

'The main reason to ascertain whether baboons are susceptible to infection with hepatitis C virus (HCV) is the need to replace chimpanzees, which are endangered, as an animal model for undertaking research into the biology and host-virus interactions of HCV, and for developing a vaccine against this virus. A second reason is that baboons are a possible source of xenografts for human liver transplantation. We innoculated serum containing HCV into four Chacma baboons and monitored them for 52 weeks for evidence of infection. Serum was tested for antibody to HCV, HCV RNA, and aminotransferase concentrations at 2-week intervals for 26 weeks and thereafter at 4 week intervals. Liver tissue was examined at 28 and 52 weeks for histopathological changes and viral RNA, and at 52 weeks for viral particles using electron microscopy. Reverse transcription-polymerase chain reaction assay was used to detect HCV RNA, and the results were confirmed by Southern hybridization. Serum aminotransferase concentrations remained within the normal range and liver histology was normal during the follow-up period. Passive transmission of anti-HCV to the baboons was observed during the first 4 weeks. HCV RNA was not detectable in any serum or liver sample and electron microscopy failed to reveal viral particles in liver tissue. In conclusion, we cannot deny that in an immunosuppressed liver transplant recipient, infection of a baboon xenograft might occur. Another animal model for HCV infection must be sought.'

Journal of Clinical Investigation (Jan. 2002) 109:221

Primary Hepatocytes of Tupaia belangeri as a Potential Model for Hepatitis C Virus Infection

'A recent pilot study has demonstrated that T. belangeri can be infected with HCV in vivo [Virology(1998)244:513]. In this study, we demonstrated that primary Tupaia hepatocytes represent a novel cell culture model for the study of HCV infection that allows for the functional assessment of HCV receptor candidate CD81....Our data suggests that HCV may use an additional receptor or receptors for viral attachment.'

Proclamations of the National Academy of Sciences, USA (1999) 96:11878

Imino Sugars Inhibit the Formation and Secretion of Bovine Viral Diarrhea Virus: Implications for the Development of Broad Anti-Hepatitis Agents

'One function of N-linked glycans is to assist in the folding of glycoproteins by mediating interactions of the lectin-like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the alpha-glucosidases, such as N-butyl-deoxynojirimycin (NB-DNJ) and N-nonyl-DNJ (NN-DNJ), and this causes some proteins to be misfolded and retained within the endoplasmic reticulum (ER).....Because viral secretion is selectively hypersensitive to glucosidase inhibition relative to the secretion of cellular proteins, the possibility that glucosidase inhibitors could be used as broad-based antiviral hepatitis agents is discussed.'

Journal of Virology (1998) 72:3851

Involvement of Endoplasmic Reticulum Chaperones in the Folding of Hepatitis C Virus Glycoproteins

'The effect of the co-overexpression of each chaperone on the folding of HCV glycoproteins was also analyzed. However, the levels of native E1-E2 complexes were not increased. Together, our data suggest that calnexin plays a role in the productive folding of HCV glycoproteins whereas calreticulin and BiP are probably involved in a nonproductive pathway of folding.'

Virology (2000) 273:60

Hepatitis C Virus Glycoprotein E2 Binding to CD81: The Role of E1-E2 Cleavage and Protein Glycosylation in Bioactivity

'Furthermore, E2 protein expressed in insect cells in the presence of N-butyldeoxynojirimycin, an inhibitor of terminal glucose residue processing, formed complexes with E1 and bound to CD81-EC2 similarly to untreated protein. Together these data suggest that although hyperglucosylation of E2 does not have a major effect on bioactivity, polyprotein processing to reveal the free amino terminus is required.'

Proclamations of the National Academy of Sciences, USA (1990) 87:2057

Hepatitis C Virus Shares Amino Acid Sequence Similarity with Pestiviruses and Flaviviruses as well as Members of Two Plant Virus Supergroups

'We report here that HCV shares an even greater degree of protein sequence similarity with members of the pestivirus group (i.e., bovine viral diarrhea virus and hog cholera virus), which are thought to be distantly related to the flaviviruses. In addition, we find that HCV shares significant protein sequence similarity with the polyproteins encoded by members of the picornavirus-like plant virus supergroups. These data suggest that HCV may be evolutionarily related to both plant and animal viruses.'

Nature (Oct. 1983)305:827

Sequence Homology between Retroviral Reverse Transcriptase and Putative Polymerases Of Hepatitis B Virus and Cauliflower Mosaic Virus

'More recently it has been suggested that the replication cycle of a plant virus, cauliflower mosaic virus (CaMV), includes a reverse transcription step.'

Vet. Rec. (1982) 111:323

Picorna-Like Virus Causing Hepatitis and Pancreatitis in Turkeys

Archives of Virology (1998) 143:127

Analysis of Genetic Information of an Insect Picorna-Like Virus, Infectious Flacherie Virus of Silkworms: Evidence for Evolutionary Relationships Among Insect, Mammalian and Plant Picorna-Like Viruses

'Computer analysis identified the sequences similar to the concensus sequences of 2C (helicase?), 3C (protease), and 3D (RNA polymerase) conserved among mammalian and plant picorna-like viruses...Further analysis of the characteristics of the genome structure and a tentative phylogenetic tree constructed on the basis of the amino acid sequence emphasized the evolutionary relationships among the insect and plant viruses.'

Current Pharmaceutical Biotechnology (2000) 1:347

N-Glycosylation of Recombinant Pharmacological Glycoproteins Produced in Transgenic Plants: Towards a Humanization of Plant N-Glycans

'Most therapeutic proteins are glycoproteins and N-glycosylation is often essential for their stability, folding, and biological activity. Recombinant glycoproteins of mammalian origin expressed in transgenic plants largely retain their biological activity. However, plants are not ideal for production of pharmacological proteins because they produce molecules with glycans that are not compatible with therapeutic applications in humans.'

Carbohydrate Research (1994) 259:243

N-Containing Sugars from Morus alba and their Glycosidase Inhibitory Activity

'These N-containing sugars are 1-deoxynojirimycin(1), N-methyl-1-deoxynojirimycin(2), fagomine(3), 3-epi-fagomine(4), 1,4,-dideoxy-1,4-imino-D-arabinitol(5)....'

Molecular Pharmacology (Jan. 2002) 61:186

The Alpha-Glucosidase Inhibitor 1-Deoxynojirimycin Blocks Human Immunodeficiency Virus Envelope Glycoprotein-Mediated Membrane Fusion at the CXCR4 Binding Step

'1-Deoxynojirimycin (DNM) is a saccharide decoy that inhibits cellular alpha-glucosidase I-II activity....These results are consistent with the inhibition by DNM of virus entry at the Env/coreceptor interaction step. Finally, preliminary data indicate that suboptimal concentrations of DNM and natural or synthetic CXCR4 ligands used in combination potently inhibit the envelope-mediated membrane fusion process. Altogether, our results suggest that DNM and its analogues deserve further investigation as anti-HIV agents in combination with experimental compounds targeting CXCR4 to inhibit each partner of this crucial step of HIV entry.'

Arch. Pharm. Res. (1999) 22:9

Purification and Characterization of Moran 20K from Morus alba

'A new glycoprotein was purified from the aqueous methanolic extract of the root bark of Morus alba which has been used as a component of an antidiabetic remedy in Oriental Medicine....The amino acid composition of the protein was analyzed, and the protein contained above 20% serine and cysteine such as in insulin.'

Biosci. Biotechnol. Biochem. (Aug. 2000)64:1664

Sulfated Fibroin, A Novel Sulfated Peptide Derived from Silk, Inhibits Human Immunodeficiency Virus Replication in Vitro

'We prepared two kinds of sulfated silk fibroins, SclFib30 and SclFib31, which contain different amounts of sulfate. These sulfated silk fibroins have anti-HIV-1 activity in vitro, apparently due to interference with the absorption of virus particles to CD4+ cells, and completely blocked virus binding to the cells at a concentration of 100 microg/ml. Sulfated fibroins also abolished cell-to-cell infection-induced synctium formation upon cocultivation of MOLT-4 and MOLT-4/HIV-III cells, suggesting that they would interfere with gp120 and prevent the formation of gp120/CD4 complex. Silk is used in biomaterials such as surgical sutures and is believed to be a safe material for humans. In accordance with low anticoagulant activity and high anti-HIV-1 activity against both X4 HIV-1 and R5 HIV-1 strains, sulfated silk fibroins have potential as antiviral material such for a vaginal anti-HIV-1 formulation.'

J. of Virological Methods (1990)35:159

High Level Expression and Characterization of Hepatitis B Virus Surface Antigen in Silkworm Using a Baculovirus Vector

'These products, consisting of two polypeptides with molecular weights of approximately 25,000 (p25) and glycosylated P25 (GP25) were purified as assembled 22-nm particles. We demonstrated that HBsAG from silkworms consists of S protein with 7 amino acids of Pre-S2.'

J. Vet. Med. Sci. (1993)55:251

Homogeneous Production of Feline Interferon in Silkworm by Replacing Single Amino Acid Code in Signal Peptide Region in Recombinant Baculovirus and Characterization of the Product

'In a previous paper we reported that we constructed a recombinant baculovirus named BmFelFN1 which produced recombinant feline interferon (FeIFN) in silkworms after infection. High purification of FeIFN in body fluid from the larvae revealed that two kinds of FeIFN were produced by the BmFeIFN1. The difference between the two in the NH2-terminal amino acid sequence was clarified, and two kinds of processing at different sites in FeIFN precursor were suggested.'

J. Interferon Cytokine Research (Nov. 2000)20:1015

Production of Canine IFN-gamma in Silkworm by Recombinant Baculovirus and Characterization of the Product

'Canine interferon-gamma (CaIFN-gamma) cDNA was expressed in silkworms by infecting recombinant baculovirus....Genetic engineering of CaIFN-gamma to remove potential glycosylation sites resulted in reduced components of the CaIFN-gamma, suggesting that one cause of this heterogeneity was glycosylation. Nonglycosylated CaIFN-gamma produced in silkworms still had several components that were deleted at the carboxy-terminal end....CaIFN-gamma showed antiviral activity, and antiproliferation activity on tumor cells.'

Biochem. Biophys. Res. Commun. (April 2000) 29:186

Silkworm Hemolymph Inhibits Baculovirus-induced Insect Cell Apoptosis

'The addition of silkworm hemolymph into culture medium either before or during the baculovirus infection increased the host cell longevity; however its addition after the infection was less effective.'

Biological Pharmaceutical Bulletin (May 1997) 20:547

Antiviral Substance from Silkworm Faeces: Purification and its Chemical Characteristics

'In a previous paper, we reported that an extract of silkworm faeces has a marked antiviral activity on enveloped viruses, but not on non-enveloped virus, and we showed that it inhibits the synthesis of a viral specific gene of HVJ (Sendai virus) without affecting the viral absorption and entry into the host cell.'

Zhongguo Yao Li Xue Bao (Aug. 1999)

Antiviral Effects of rhIFN-alpha 1 Against Seven Influenza Viruses

'The inhibitory rates of of rhIFN-alpha 1 (Chinese silkworm gene recombinant interferon alpha 1) to pulmonary-indice were 14.8%-37.4%. Conclusion: rhIFN-alpha-1 inhibited the proliferation of influenza virus and improved the symptom of mouse pneumonia caused by influenza virus.'

Journal of Virology (2001) 75:3527

Antiviral Effects of N-Butyldeoxynojirimycin Against Bovine Viral Diarrhea Virus Correlates with Misfolding of E2 Envelope Proteins and Impairment of Their Association into E1-E2 Heterodimers

'In this report, we investigate the molecular mechanism of this inhibition by studying the folding pathway of BVDV enveloped glycoproteins in the presence and absence of NB-DNJ. Our results show that, while the disulfide-dependent folding of E2 glycoprotein occurs rapidly (2.5 min.), the folding of E1 occurs slowly (30 min.).'

Nature Medicine (1998) 4:610

Treatment of Chronic Hepadnavirus Infection in a Woodchuck Animal Model with an Inhibitor of Protein Folding and Trafficking

'The exquisite sensitivity of HBV to alterations in the envelope proteins induced by alpha-glucosidase inhibitors might allow anti-viral doses that do not affect host glycosylation. Here we report proof of this concept in a woodchuck animal model of HBV infection....N-nonyl-DNJ is the 9-carbon alkyl derivative of deoxynojirimycin (DNJ) and has been shown to be 100-200 times more potent than N-butyl-deoxynojirimycin (NB-DNJ) in inhibiting cell based assays. There was no clinical, biochemical or hematological evidence of drug toxicity and the body weights of N-nonyl-DNJ-treated woodchucks were similar to placebo treated controls.'

Zhongguo Xhong Yao Za Zhi (1998) 23:363

Chemical Constituents of Phyllanthus urinaria L. and its Antiviral Activity Against Hepatitis B Virus

'Eleven compounds have been isolated. Two of them are new compounds, methyl ester dehydrochebulic acid and methyl brevifolin carboxylate. Antiviral experiments on HBsAG in vitro and liver damage caused by CCL4 have shown that Phyllanthus urinaria possesses antiviral activities against HBV.'

Tetrahedron (1999) 55:5781

Leaf-Movement Factor of Nyctinastic Plant, Phyllanthus urinaria L. The Universal Mechanism for the Regulation of Nyctinastic Leaf Movement

'Phyllanthurinolactone(1) and phyllurine(2), were isolated from Phyllanthus urinaria as bioactive substances for nyctinasty....The concentration of (1) increased before leaf closure in the plant body, whereas that of (2) was constant through a day. Thus, the leaf-movement of Phyllanthus urinaria is proposed to be controlled by the change in the balance of concentration between (1) and (2) which is regulated by a beta-glucosidase, similar to the case of Lespedeza cuneata G. Don.

Most Legumonisae plants close their leaves in the evening, as if to sleep, and open them in the morning. This is called nyctinastic movement, and is known to be controlled by a biorhythm of the plant regulated by its biological clock. The discovery of a biological clock was based on the observation of nyctinastic movement in Mimosa pudica L. In the 18th century, a French scientist discovered that rhythm involved in nyctinastic leaf-movement was maintained even under continuous darkness in a cave.

And we shall advance the universal mechanism of the control of nyctinasty, which can explain all nyctinastic movement by only one key-word, that is, the control of the beta-glucosidase activity by a biological clock.'

Journal of Virology (2002):1265

Detection of a Novel Unglycosylated Form of Hepatitis C Virus E2 Envelope Protein that is Located in the Cytosol and Interacts with PKR

'The hepatitis C virus (HCV) envelope protein E2 has been shown to accumulate in the lumen of the endoplasmic reticulum (ER) as a properly folded glycoprotein as well as large aggregates of misfolded proteins. In the present study, we have identified an additional unglycosylated species, with an apparent molecular mass of 38kDA (E2-p38). In contrast to the glycosylated E2, E2-p38 is found to be ubiquinated. E2-p38 is localized mostly in the cytosol, in contrast to the glycosylated form, which is exclusively membrane associated. Alpha interferon (IFN-alpha) treatment or overexpression of the double-stranded RNA-activated protein kinase (PKR) significantly increased the stability of E2-p38, consistent with a previous report [Science 285:107] that E2 interacts with PKR and inhibits its kinase activity. Direct interaction between PKR and E2-p38, but not the glycosylated form of E2, was also observed.

These results show that E2-p38 is the form of E2 that interacts with PKR in the cytosol and may contribute to the resistance of HCV to IFN-alpha. Thus, an ER protein can exist in the cytosol as an unglycosylated species and impair cellular functions.

Since IFN upregulates PKR, this affect was most likely due to the interaction of E2-p38 with PKR, which, as a result, prevents its degredation by the proteosome. Indeed, we found that PKR binds to the unglycosylated but not the glycosylated form of E2. These results solved the puzzling question of how E2 which was thought to reside exclusively in the lumen of the ER, could interact with PKR, which is in the cytosol as well as associated with ribosome. Furthermore, it shows that viral glycoproteins can be found in various forms and thus have other unexpected functions in the cells than just being on the virion surface to interact with cellular receptors.'

Molecular Psychiatry (Nov. 2001)6:701

A Novel Mechanism to Explain Protein Abnormalities in Schizophrenia Based on the Flavivirus Resistance Gene

'The geographical distribution of schizophrenia was previously shown to correlate with the global distribution of tick-borne flaviviruses. The correlation suggests a natural resistance gene to flaviviruses could be involved in schizophrenia....Although the sequence and product of Flv are unknown, translation elongation factor alpha-1 (EF-1) is a protein known to interact with the 3' UTR flavivirus RNA, forming some complexes with long half-lives that inhibit RNA growth. A study was performed to assess the homology between flaviviral UTRs, subunits of EF-1, and selected proteins reported as abnormal in schizophrenia. The UTRs of four flaviviruses with wide geographical and phylogenetic distribution were manually translated. Using the National Biochemical Research Foundation protein databank, the amino acid sequences were correlated with the amino acid sequences of selected proteins. The amino acid sequences of the EF-1 subunits were then correlated with the same proteins. Similar amino acid correlations between the proteins, EF-1 subunits, and viral UTRs suggest that translational pathophysiology resulting from the product of Flv can be postulated as the cause of protein abnormalities observed in schizophrenia.'

Current Opinions in Plant Biology (1998) 1:434

Mechanism of Auxin Action

'The plant growth hormone auxin has an important role in a variety of plant growth and developmental processes. Identification of transcriptional factors, some with defined genetic function, have shed new light on the mechanisms of auxin-regulated gene expression. In addition, the molecular characterization of genes required for auxin response indicates that regulated protein degredation by the ubiquitin-proteosome pathway has an important function in auxin action.'

J. Virology (April 2002)76:3570

Inhibition of Hepatitis B Virus Replication by Interferon Requires Proteosome Activitydagger

'Hepatitis B virus (HBV) replication is inhibited in a noncytopathic manner by alph/beta interferon (IFN-alpha/beta) and IFN-gamma. We demonstrate here that inhibitors of cellular proteosome activity can block this antiviral effect. These results suggest that a critical component of the IFN-induced antiviral response may be the proteosome-dependent degredation of viral or cellular proteins that are required for HBV replication.'

Zhong Xi Yi Jie He Za Zhi (Sept. 1990)10:560

Anti-HBsAG Herbs Employing ELISA Techniques

'With the aid of the ELISA system this schema represented a laboratory approach to the recognition of anti-HBsAG capability of herbs by using 300 herbal extracts. Altogether 10 herbs were identified as effective....The ten effective herbs were listed in the following order: Prunella vulgaris (1.00), Litchi chinensis (1.26), Gossypium herbaceum (1.45), Cudrania cochinchinensis (1.56), Caesalpinia sappan (1.73), Oldenlandia tenelliflora (1.77), Cautis parthenocissus (1.99), Evodia rutaecarpa (2.01), Portulaca grandiflora (2.44), and Anemone hupehensis (2.83).'

Planta Medica (May 2000)66:358

Anti-allergic and Anti-inflammatory Triterpenes from the Herb Prunella vulgaris

'The activity-guided fractionation of the extract of the herb Prunella vulgaris (Labiatae) led to the isolation of four triterpenes, i.e., betulinic acid, ursolic acid, 2-alpha, 3-alpha-dihydroxyurs-12-en-28-oic acid, and 2-alpha-hydroxyursolic acid. One of these compounds, 2-alpha, 3-alpha-dihydroxyursolic acid, demonstrated significant inhibition on the release of beta-hexosaminidase from the cultured RBL-2H3 cells in a dose-dependent manner....When the isolated compounds were tested for their effects on the production of nitric oxide from cultured murine macrophages, RAW 264.7 cells, ursolic acid and 2-alpha-hydroxyursolic acid exhibited strong inhibitory activities (IC50 values, 17 and 27 microM, respectively).'

Antiviral Chemistry and Chemotherapy (Mar. 2000) 11:157

Extract of Prunella vulgaris Spikes Inhibits HIV Replication at Reverse Transcription in Vitro and Can Be Absorbed from Intestine in Vivo

'The activity of PS (spike) extract in the cells was also assessed by the drug addition test, during and after HIV adsorption. PS extract and dextran sulfate suppressed HIV production to similar levels when added after HIV adsorption. However, only PS extract suppressed HIV production at the same concentration when the drugs were added during HIV adsorption. Presumably, the penetration of the PS extract into the cells was required for this activity. Secondly, fractionated PS inhibited HIV reverse transcription in a non-competetive manner. The fractionated PS kept anti-HIV activity, but inhibited HIV replication and adsorption to a lesser extent compared to dextran sulfate. Lastly, an active component(s) was detected in plasma in vivo, after injection into the intestine, which demonstrates the feasibility of oral administration dosing.'

Virology (Mar. 1992)187:56

Mechanism of Inhibition of HIV-1 Infection in Vitro by Purified Extract of Prunella vulgaris

'Crude extracts of four Chinese herbs, Arctium lappa, Astragalus membranaceus, Andrographis paniculata, and Prunella vulgaris, were assessed in several tissue culture lines for anti-HIV-1 activity and for cytotoxicity.'

Zhonghua Liu Xing Bing Xue Za Zhi (April 1991)12:83

Serologic Investigation of HBV in 302 Patients Who Had a History of Smallpox

'This paper provides serologic investigation of HBV in 302 persons who had history of smallpox in Zhumadian County. The results showed that the HBsAG positivity rate (1.3%) was significantly lower than those of the control group 1 (8.3%) and 2 (8.6%) (P less than 0.001). The HBV infection rate was also lower than those of the control group 1 (47.7%) and 2 (51.3%) (P less than 0.001). There was not much difference between the two control groups. The determination of cellular immunity showed the rosette positivity rate (75.93%) and lymphocyte conversion rate (70.39%) of the patients' group were higher than those of control group 1 (62.3% and 52.9%) and 2 (60.93% and 55.3%). It may be suggested that patients having had smallpox might have enhanced cellular immunity which might interfere with HBV infection.'

J. Virology (Feb. 2002)76:1932

Single Mutation in the Flavivirus Envelope Protein Hinge Region Increases Neurovirulence for Mice and Monkeys but Decreases Viscerotropism for Monkeys: Relevance to Development and Safety Testing of Live, Attenuated Vaccines

'In independent transfection-passage studies with FRhl or Vero cells, mutations appeared most frequently in hinge 4 (bounded by amino acids E266 to E284), reflecting genome instability in this functionally important region....Based on sensitivity and comparability of results with those for monkeys, the suckling mouse is an appropriate host for safety testing of flavivirus vaccine candidates for neurotropism. After intracerebral innoculation, the E279 Lys virus was restricted with respect to extraneural replication in monkeys, as viremia and antibody levels (markers of viscerotropism) were significantly reduced compared to those for the E279 Met virus. These results are consistent with the observation that empirically derived vaccines developed by mouse brain passage of dengue and YF viruses have increased neurovirulence for mice but reduced viscerotropism for humans.'

Vopr. Virusol. (Mar.-Apr. 1990)35:132 (Article in Russian)

Verification of the Safety, Inoculability, Reactogenicity and Antigenic Properties of a Live Recombinant Smallpox-Hepatitis B Vaccine in an Experiment in Volunteers

'Trials of the first Soviet Live Recombinant Smallpox-Hepatitis B Vaccine (SHBV) in volunteers (20 men aged 18-20 years) showed its safety, good 'take' rate, and lower reactogenicity as compared with the standard smallpox vaccine (LIVP strain). Smallpox virus-neutralizing antibodies in response to SHBV were produced as well as in response to the smallpox vaccine. Revaccination of human subjects with smallpox vaccine and SHBV 45 days after the previous vaccination resulted in antibody booster to vaccinia virus. After two inoculations of SHBV at an interval of 45 days no anti-HBsAG antibodies were found for 3 months after the last vaccination. However, a single vaccination with SHBV induced priming to HBsAG. This could be demonstrated after inoculation of the subjects vaccinated with SHBV with one dose of plasma hepatitis vaccine. In the subjects vaccinated with SHBV antibody in response to the plasma vaccine formed more frequently and in higher titres than in those prevaccinated with smallpox vaccine or placebo.'

March 15, 2002, 2:20 A.M. Wind moderate, cloud-streets moving NW.