Showing papers on "Virus published in 1985"

3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro.

Abstract: The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.

Heritable formation of pancreatic β -cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes

Abstract: Following the transfer into fertilized mouse eggs of recombinant genes composed of the upstream region of the rat insulin II gene linked to sequences coding for the large-T antigen of simian virus 40, large-T antigen is detected exclusively in the beta-cells of the endocrine pancreas of transgenic mice. The alpha- and delta-cells normally found in the islets of Langerhans are rare and disordered. Well-vascularized beta-cell tumours arise in mice harbouring and inheriting these hybrid oncogenes.

Structure of a human common cold virus and functional relationship to other picornaviruses

Abstract: We report the first atomic resolution structure of an animal virus, human rhinovirus 14. It is strikingly similar to known icosahedral plant RNA viruses. Four neutralizing immunogenic regions have been identified. These, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on external protrusions. A large cleft on each icosahedral face is probably the host cell receptor binding site.

The hepatitis B virus

Abstract: DNA recombinant technology has radically changed hepatitis B virus (HBV) virology. The genetic organization, transcription and replication of the virus are basically understood, structures of integrated HBV sequences in hepatocellular carcinoma have been characterized, and new vaccines produced by recombinant DNA technique are being developed.

Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide.

Abstract: Comparative surface feature analyses of the VP1 sequences of hepatitis A virus (HAV) and poliovirus type 1 allowed an alignment of the two sequences and an identification of probable HAV neutralization antigenic sites. A synthetic peptide containing the HAV-specific amino acid sequence of one of these sites induced anti-HAV-neutralizing antibodies. It is concluded that a structural homology exists between the two viruses, despite minimal primary sequence conservation.

Isolation of T-cell tropic HTLV-III-like retrovirus from macaques

Abstract: The isolation of a T-cell tropic retrovirus from three immunodeficient macaques and one macaque with lymphoma is described. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of acquired immune deficiency syndrome in humans (HTLV-III or LAV). This virus is referred to as simian T-lymphotropic virus type III (STLV-III) of macaques. The existence of a cytopathic, T-cell tropic virus resembling HTLV-III in monkeys may facilitate study of disease induction and vaccine development in an animal model.

Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution

Abstract: The sequence of the entire RNA genome of the type flavivirus, yellow fever virus, has been obtained. Inspection of this sequence reveals a single long open reading frame of 10,233 nucleotides, which could encode a polypeptide of 3411 amino acids. The structural proteins are found within the amino-terminal 780 residues of this polyprotein; the remainder of the open reading frame consists of nonstructural viral polypeptides. This genome organization implies that mature viral proteins are produced by posttranslational cleavage of a polyprotein precursor and has implications for flavivirus RNA replication and for the evolutionary relation of this virus family to other RNA viruses.

Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity

Abstract: Amino acid sequence homology was found between viral and host encephalitogenic protein. Immune responses were then generated in rabbits by using the viral peptide that cross-reacts with the self protein. Mononuclear cell infiltration was observed in the central nervous systems of animals immunized with the viral peptide. Myelin basic protein (MBP) is a host protein whose encephalitogenic site of ten amino acids induces experimental allergic encephalomyelitis. By computer analysis, hepatitis B virus polymerase (HBVP) was found to share six consecutive amino acids with the encephalitogenic site of rabbit MBP. Rabbits given injections of a selected eight- or ten-amino acid peptide from HBVP made antibody that reacted with the predetermined sequences of HBVP and also with native MBP. Peripheral blood mononuclear cells from the immunized rabbits proliferated when incubated with either MBP or HBVP. Central nervous system tissue taken from these rabbits had a histologic picture reminiscent of experimental allergic encephalomyelitis. Thus, viral infection may trigger the production of antibodies and mononuclear cells that cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoallergic event can take place in the absence of the infectious virus that initiated the immune response.

Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay

Abstract: The human T-cell lines MT-2 and MT-4 carry the human T-cell leukemia virus type I (HTLV-I). When MT-2 and MT-4 were infected with HTLV-III, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS), rapid cytopathogenic effects and cytotoxicity were observed that made it possible to titrate the biologically active virus in a plaque-forming assay. The cytopathogenic effects were preceded by the rapid induction and increase of HTLV-III antigens as revealed by immunofluorescence and immunoprecipitation. Activities of HTLV-III were neutralized by the human antibodies against the virus when immunofluorescence and plaque assays were used. Essentially the same results were obtained with the lymphadenopathy-associated virus (LAV1).

HTLV-III infection in brains of children and adults with AIDS encephalopathy

Abstract: Unexplained debilitating dementia or encephalopathy occurs frequently in adults and children with the acquired immune deficiency syndrome (AIDS). Brains from 15 individuals with AIDS and encephalopathy were examined by Southern analysis and in situ hybridization for the presence of human T-cell leukemia (lymphotropic) virus type III (HTLV-III), the virus believed to be the causative agent of AIDS. HTLV-III DNA was detected in the brains of five patients, and viral-specific RNA was detected in four of these. In view of these findings and the recent demonstration of morphologic and genetic relatedness between HTLV-III and visna virus, a lentivirus that causes a chronic degenerative neurologic disease in sheep, HTLV-III should be evaluated further as a possible cause of AIDS encephalopathy.

Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques.

Abstract: We constructed a plasmid coexpression vector that directs the insertion of a foreign gene of interest together with the Escherichia coli beta-galactosidase (beta gal) gene into the thymidine kinase (TK) locus of the vaccinia virus genome. Tissue culture cells that had been infected with vaccinia virus were transfected with a plasmid vector containing a foreign gene. TK- recombinants could be selected by a plaque assay on TK- cells in the presence of 5-bromodeoxyuridine and distinguished from spontaneous TK- mutants by the addition of a beta-gal indicator to the agarose overlay. Plaques that expressed beta-gal stained dark blue within several hours at 37 degrees C. Alternatively, TK- selection could be eliminated, and recombinant plaques could be readily identified solely by their blue color. The reverse procedure, in which the starting virus expresses beta-gal (i.e., forms blue plaques) and the desired recombinant has deleted the entire beta-gal gene (i.e., forms white plaques), is another alternative. Each protocol was tested by constructing vaccinia virus recombinants that express hepatitis B virus surface antigen.

Replication of Epstein–Barr Virus within the Epithelial Cells of Oral Hairy Leukoplakia, an AIDS-Associated Lesion

Abstract: We conducted a study to identify the viruses in tissue specimens of oral "hairy" leukoplakia, a lesion that is found in immunosuppressed male homosexuals and that is associated with the subsequent development of the acquired immunodeficiency syndrome. When stained for papillomavirus core antigen, 49 of 67 biopsy specimens (73 per cent) yielded positive results in epithelial-cell nuclei. Electron microscopy showed papillomavirus-like particles in all of 25 specimens, and the herpes-type virus described in a previous report was seen in 23 of the 25 specimens. Three specimens had both types of particle in the same individual epithelial cells. Immunofluorescence for herpes simplex virus, varicella-zoster virus, and cytomegalovirus gave negative results in all cases, but 19 of 20 specimens showed intense nuclear staining in epithelial cells for the viral capsid antigen of Epstein-Barr virus (EBV). DNA hybridization using EBV probes in Southern blots demonstrated EBV DNA in all of 13 specimens and found 200 or more viral DNA molecules per cellular genome in 11 of the 13. The whole EBV genome was also demonstrated in the specimens and found to be in linear virion form. We conclude that EBV replicates within the epithelial cells in hairy leukoplakia.

Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus.

Abstract: The 9,213-nucleotide structure of the AIDS/lymphadenopathy virus has been determined from molecular clones representing the integrated provirus and viral RNA. The sequence reveals that the virus is highly polymorphic and lacks significant nucleotide homology with type C retroviruses characterized previously. Together with an analysis of the two major viral subgenomic RNAs, these studies establish the coding frames for the gag, pol and env genes and predict the expression of a novel gene at the 3' end of the genome unrelated to the X genes of HTLV-1 and -II.

The molecular basis of the specific anti-influenza action of amantadine.

Abstract: Amantadine (1-aminoadamantane hydrochloride) is effective in the prophylaxis and treatment of influenza A infections. In tissue culture this selective, strain-specific antiviral activity occurs at relatively low concentrations (5 microM or less), which inhibit either the initiation of infection or virus assembly. The data reported here demonstrate that the basis of these actions is similar and resides in the virus-coded M2 membrane protein, the product of a spliced transcript of RNA segment 7. Mutations which confer resistance to amantadine are restricted to four amino acids within a hydrophobic sequence, indicating that the drug is targetted against the putative membrane-associated portion of the molecule. The influence of the virus haemagglutinin on the amantadine sensitivity of virus strains implies that the drug may interfere with interactions between these two virus proteins.

Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4.

Abstract: Using Vero cells transformed with the wild-type gene for ICP4 as the permissive host cell, we isolated herpes simplex virus type 1 (HSV-1) mutants containing deletions in both copies of the ICP4 gene The mutants, d120 and d202, contained deletions of 41 and 05 kilobases, respectively, in each copy of ICP4 ICP4 mRNA synthesized in d202-infected Vero cells was 05 kilobases smaller than that synthesized in cells infected with the wild-type virus No ICP4 mRNA was detected in d120-infected Vero cells d120 and d202 specified polypeptides that reacted with ICP4 antiserum and were smaller than the wild-type ICP4 polypeptide by 130 and 30 kilodaltons, respectively The only other HSV-1 gene products detectable on infection of Vero cells with d120 and d202 were ICP6 (of the early kinetic class of HSV-1 polypeptides), ICP0 (immediate early), ICP22 (immediate early), and ICP27 (immediate early) Immediate-early polypeptides ICP0 and ICP27 were expressed to a higher level in Vero cells infected with an ICP4 temperature-sensitive (ts) mutant (tsB32) at 39 degrees C, indicating immediate-early stimulatory activity associated with the ts ICP4 polypeptide In addition, the patterns of complementation of d120, d202, and tsB32 in ICP4-transformed cells also demonstrated inhibitory activity associated with the ts form of the ICP4 polypeptide

Two distinct subtypes of human respiratory syncytial virus.

Abstract: Antigenic variation of human respiratory syncytial (RS) virus strains was analysed using a collection of nine, six, six, nine and one monoclonal antibodies respectively directed against the large glycoprotein (G), fusion protein (F), matrix protein (M), nucleoprotein (NP) and phosphoprotein (P) components of the Long strain of RS virus. A comparison was made with seven other strains isolated during different years in radioimmune precipitation analyses and immune fluorescence tests. Two different subtypes of the virus were demonstrable. Subtype A included the prototype strains Long and A2 and virus isolates from 1973, 1983 and 1984; subtype B included four virus strains isolated in successive years from 1979 to 1982. Subtype A viruses reacted with all the antibodies, whereas subtype B viruses showed different epitope characteristics in four structural components. The number of altered epitopes were 5/6, 1/2, 2/6 and 1/6 in the G, F, M and NP components, respectively. It is concluded that the two subtypes have evolved separately. The finding of two subtypes may explain previously observed strain variations in neutralization tests, and gives a new perspective on the immunobiology of RS virus.

Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III

Abstract: Antibodies from the serum of patients with the acquired immune deficiency syndrome (AIDS) or with the AIDS-related complex and from the serum of seropositive healthy homosexuals, recognize two major glycoproteins in cells infected with human T-cell lymphotropic virus type III (HTLV III). These glycoproteins, gp160 and gp120, are encoded by the 2.5-kilobase open reading frame located in the 3' end of the HTLV-III genome, as determined by amino terminus sequence analysis of the radiolabeled forms of these proteins. It is hypothesized that gp160 and gp120 represent the major species of virus-encoded envelope gene products for HTLV-III.

Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III.

Abstract: The retrovirus involved in acquired immune deficiency syndrome (HTLV-III/LAV) contains a region that is necessary for stimulation of gene expression directed by the viral long terminal repeat. This region is located between nucleotides 5365 and 5607, immediately 59 to the envelope gene. A doubly-spliced message containing this region could encode an 86-amino acid protein with structural features similar to those of nucleic acid-binding proteins.

Antiviral effect of flavonoids on human viruses.

Abstract: The effect of several naturally occurring dietary flavonoids including quercetin, naringin, hesperetin, and catechin on the infectivity and replication of herpes simplex virus type 1 (HSV-1), polio-virus type 1, parainfluenza virus type 3 (Pf-3), and respiratory syncytial virus (RSV) was studied in vitro in cell culture monolayers employing the technique of viral plaque reduction. Quercetin caused a concentration-dependent reduction in the infectivity of each virus. In addition, it reduced intracellular replication of each virus when monolayers were infected and subsequently cultured in medium containing quercetin. Preincubation of tissue culture cell monolayers with quercetin did not affect the ability of the viruses to infect or replicate in the tissue culture monolayers. Hesperetin had no effect on infectivity but it reduced intracellular replication of each of the viruses. Catechin inhibited the infectivity but not the replication of RSV and HSV-1 and had negligible effects on the other viruses. Naringin had no effect on either the infectivity or the replication of any of the viruses studied. Thus, naturally occurring flavonoids possess a variable spectrum of antiviral activity against certain RNA (RSV, Pf-3, polio) and DNA (HSV-1) viruses acting to inhibit infectivity and/or replication.

Persisting Illness and Fatigue in Adults with Evidence of Epstein-Barr Virus Infection

Abstract: Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. However, 20 patients had abnormal serologic profiles specific for Epstein-Barr virus shown by significantly elevated titers of antibodies to the viral capsid antigen or early antigen, or by a deficiency of late-appearing antibodies. In 11 of 15 patients tested, circulating immune complexes were found. Circulating interferon was not found in 18 patients tested, but the activity of 2-5 oligoadenylate synthetase, an interferon-induced enzyme, was increased in 5 patients studied. Of 19 patients, 18 had persisting suppressor T-cell activity typically found in patients recovering from acute infectious mononucleosis. We believe that the Epstein-Barr virus may be associated with chronic illness in adults.

Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes

Abstract: Influenza A virus-specific cytotoxic T lymphocytes (CTL) capable of lysing cells infected with any influenza A virus ("cross-reactive CTL") constitute a major portion of the host CTL response to influenza. The viral nucleoprotein (NP), a major internal virion structural protein, has been implicated as a possible target antigen for cross-reactive CTL. To directly examine CTL recognition of NP, a vaccinia virus recombinant containing a DNA copy of an influenza A virus NP gene was constructed. We found that murine cells infected with this virus were efficiently lysed in a major histocompatibility complex-restricted manner by cross-reactive CTL populations obtained by immunization with a variety of influenza A virus subtypes. In addition, the recombinant vaccinia virus containing the PR8 NP gene was able to both stimulate and prime for a vigorous secondary cross-reactive CTL response. Significantly, splenocytes from mice primed by inoculation with the recombinant vaccinia virus containing the PR8 NP gene could be stimulated by influenza A viruses of all three major human subtypes. Finally, unlabeled target competition experiments suggest that NP is a major, but not the sole, viral target antigen recognized by cross-reactive CTL.

Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat.

Abstract: Human T-cell leukemia virus type III (HTLV-III) was recently identified as the probable etiologic agent of the acquired immune deficiency syndrome (AIDS). Here it is shown that, in human T-cell lines infected with HTLV-III, gene expression directed by the long terminal repeat sequence of this virus is stimulated by more than two orders of magnitude compared to matched uninfected cells. The rate of transcription of the HTLV-III long terminal repeat is more than 1000 times that of the SV40 early promoter in one infected cell line. Thus, HTLV-III, like HTLV-I, HTLV-II, and the bovine leukemia virus, is characterized by trans-activation of transcription in infected cells. The efficiency of trans-activation in the case of HTLV-III may account, at least in part, for the virulent nature of HTLV-III infection.

Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype

Abstract: Recent advances in molecular genetics have led to the possibility of using large DNA viruses, such as vaccinia virus, as a biological delivery system for immunizing man against unrelated disease-causing agents. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg), the influenza A virus haemagglutinin, the herpes simplex virus (HSV) type 1 D glycoprotein, the rabies virus G glycoprotein and the vesicular stomatitis virus G glycoprotein were used for immunization, animals were protected upon challenge with the appropriate pathogenic agent. A major concern with using such vaccines, however, stems from the previously documented vaccinia virus-associated post-immunizing complications. We present here experimental evidence that thymidine kinase-negative (TK-) vaccinia virus recombinants, constructed by inserting a variety of DNA coding sequences into the vaccinia virus tk gene, are less pathogenic for mice than wild-type virus.

Hepatitis b virus dna in patients with chronic liver disease and negative tests for hepatitis b surface antigen

Abstract: We assessed the presence of hepatitis B virus (HBV) DNA in liver or serum samples from 134 patients with hepatitis B surface antigen (HBsAg)-negative chronic liver disease, including 20 with hepatocellular carcinoma. HBV DNA sequences were detected in 52 of the 88 liver samples (59 per cent), including 17 of the 20 samples from patients with hepatocellular carcinoma. Presumably "replicative forms" of HBV DNA were detected in only 5 of the 88 liver samples, 3 of which were from patients with no serologic marker for HBV. In most of the liver samples the DNA patterns were consistent with the presence of HBV or a closely related virus. Of the 105 serum samples tested, HBV DNA sequences were identified in 10 (9.5 per cent), 6 of which had no HBV serologic marker. Moreover, HBsAg-associated determinants were detected in 5 of 17 patients who were positive for HBV DNA and in none of 14 patients who were negative. This study demonstrates the high frequency of HBsAg-negative HBV DNA–positive viral infectio...

Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients.

Abstract: Human T-lymphotropic virus type III (LAV, HTLV-III) is aetiologically linked to acquired immune deficiency syndrome (AIDS) and persistent general lymphadenopathy (PGL). Specific radioimmunoassays (RIA), enzyme-linked assays, immunofluorescence assays (IFA) and immunoblotting techniques are being used widely to detect serum antibodies to HTLV-III in infected patients and in those at risk of infection. However, these assays do not functionally identify those antibodies that neutralize the infectivity of the virus. We have used three methods of titrating serum neutralizing factors: inhibition of syncytium induction, neutralization of envelope pseudotypes of vesicular stomatitis virus (VSV) and reduction of infectivity of HTLV-III for a cell line permissive to virus replication. We report here that sera from subjects in various disease categories possess only low-level neutralizing activity, even when antibodies to viral membrane antigens are present in high titre. Envelope pseudotypes prepared from four HTLV-III isolates made in three different countries are equally sensitive to neutralization by positive sera, including sera from patients yielding two of the virus isolates.

African Swine Fever Virus

Abstract: African swine fever (ASF) was first described in 1921 by Montgomery, who reported several disease outbreaks of domestic pigs in Kenya since 1910 with a mortality close to 100%. Montgomery recognized the viral nature of the disease, its likely transmission by wild swine which probably acted as virus carriers, and the lack of protection by passive immunization [1]. ASF is a menace to the pig population in the world because there is no vaccine, the virus multiplies in ticks and mutates easily, and different virus isolates can produce diseases with different clinical forms or no disease at all. The control and eradication of ASF require rapid diagnosis, drastic slaughter, and quarantine.