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Biomedical subjects

S E Straus

Publications and source records attributed to S E Straus.

At least 109 records · Page 6Linked to original sources
PubMed1996

Kaposi's sarcoma (KS)-associated herpesvirus-like DNA sequences in peripheral blood mononuclear cells: association with KS and persistence in patients receiving anti-herpesvirus drugs.

Herpesvirus-like DNA sequences (KSHV/HHV-8) have recently been described in AIDS-associated Kaposi's sarcoma (KS) lesions. Many questions remain regarding the role of this virus in KS and the therapeutic implications of this finding. In the current study, KSHV/HHV-8 DNA was detected in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-infected patients with KS (34/98) more often than in HIV-infected individuals without KS (12/64, P = .03). The detection of KSHV/HHV-8 DNA did not correlate with the CD4 lymphocyte count. Five patients demonstrated KSHV/HHV-8 DNA in their PBMCs during administration of intravenous foscarnet and/or ganciclovir. The continued detection of KSHV/HHV-8 DNA in the PBMCs of patients receiving these anti-herpesvirus drugs has potential implications regarding the virus-cell relationship of KSHV/HHV-8, as well as for the value of these drugs in treating or preventing KS, but additional studies are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Protection of nude mice by passive immunization with a type-common human recombinant monoclonal antibody against HSV.

Herpes simplex viral disease is an important cause of morbidity and mortality in man. Although the development of very effective nucleoside analogs with a high therapeutic index has greatly improved the clinical management of herpetic infections, the emergence of drug-resistant viral strains has become a cause of serious concern both because of its clinical implications and in terms of viral ecology. The present report is the first demonstration of the in vivo protective activity of a type-common human recombinant monoclonal antibody derived from a combinatorial antibody library. Athymic nude mice were infected with HSV type 1 either intracutaneously in the flank or by corneal scarification. Beside reducing morality rates when administered before infection, the antibody dramatically and significantly prolonged survival times (P < 0.0001) when administered up to 24 hr postinfection, a time when the virus had already reached the peripheral nervous system. This suggests that the antibody may act, at least in part, by interfering with axonal transport of the virus and/or with viral expression. These results indicate that human recombinant antibodies isolated by antigen selection from combinatorial libraries can be effective in vivo. Such antibodies could complement antiviral chemotherapy and represent valuable tools for the prophylaxis of infections by the herpes simplex viruses.

Animals↗
PubMed1996

Periodic illness associated with Epstein-Barr virus infection.

A 15-year-old boy with a 13-year history of periodic fevers, lymphadenopathy, and leukocytosis showed virological, serological, immunohistologic, and molecular evidence of persistent, active, Epstein-Barr virus (EBV) infection. Acyclovir and several other agents failed to alter his clinical course. Comprehensive immunological studies could not identify a defined immune deficiency syndrome to explain the persistent infection, although he does continue to have circulating polymeric EBV-specific immunoglobulin type A, as is seen in individuals during acute EBV infections. In vitro work suggests that this polymeric antibody prevents B cell infection by EBV. Cumulative data suggest that this patient suffers from a novel form of EBV infection.

Adolescent↗
PubMed1996

Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression.

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force. MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal. The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects.

Adult↗
PubMed1995

Hydrophobic cluster analysis predicts an amino-terminal domain of varicella-zoster virus open reading frame 10 required for transcriptional activation.

Varicella-zoster virus open reading frame 10 (ORF10) protein, the homolog of the herpes simplex virus protein VP16, can transactivate immediate-early promoters from both viruses. A protein sequence comparison procedure termed hydrophobic cluster analysis was used to identify a motif centered at Phe-28, near the amino terminus of ORF10, that strongly resembles the sequence of the activating domain surrounding Phe-442 of VP16. With a series of GAL4-ORF10 fusion proteins, we mapped the ORF10 transcriptional-activation domain to the amino-terminal region (aa 5-79). Extensive mutagenesis of Phe-28 in GAL4-ORF10 fusion proteins demonstrated the importance of an aromatic or bulky hydrophobic amino acid at this position, as shown previously for Phe-442 of VP16. Transactivation by the native ORF10 protein was abolished when Phe-28 was replaced by Ala. Similar amino-terminal domains were identified in the VP16 homologs of other alphaherpesviruses. Hydrophobic cluster analysis correctly predicted activation domains of ORF10 and VP16 that share critical characteristics of a distinctive subclass of acidic activation domains.

Amino Acid Sequence↗
PubMed1995

Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome.

Five unrelated children are described with a rare autoimmune lymphoproliferative syndrome (ALPS) characterized by massive nonmalignant lymphadenopathy, autoimmune phenomena, and expanded populations of TCR-CD3+CD4-CD8- lymphocytes. These findings, suggesting a genetic defect in the ability of T lymphocytes to respond to normal immunoregulatory mechanisms, prompted an evaluation of lymphocyte apoptosis. Each child had defective Fas-mediated T lymphocyte apoptosis associated with a unique, deleterious Fas gene mutation. One mutation appeared to cause a simple loss of function; however, four others had a dominant negative phenotype when coexpressed with normal Fas. Family studies demonstrated the inheritance of the mutant Fas alleles. The occurrence of Fas mutations together with abnormal T cell apoptosis in ALPS patients suggests an involvement of Fas in this recently recognized disorder of lymphocyte homeostasis and peripheral self-tolerance.

Antigens, Surface↗
PubMed1995

Varicella-zoster virus gene 63: transcript mapping and regulatory activity.

The varicella-zoster virus (VZV) putative immediate-early (IE) protein encoded by ORF63 is the homolog of HSV-1 ICP-22. To further characterize ORF63 and its function, Northern analysis, primer extension, and S1 nuclease assays were used to map its transcripts, and transient transfection assays were performed with constructs containing ORF63 or its promoter region. Two transcripts were identified: a 0.9-kb transcript spans ORF63 alone, and a 1.8-kb transcript reads through ORF64. Two prominent transcription start sites were identified at -88 and -157 relative to the ORF63 ATG, and two potential TATA elements were identified. In transient transfection assays, the 63 promoter was weakly activated by VZV ORF4 and ORF62 under their homologous promoters, was more strongly activated by ORF62 under the control of a constitutive CMV promoter, and was synergistically activated by ORFs 4 and 62 together. ORF63, driven by its own or by a heterologous SV40 promoter, exerted minimal effects on diverse VZV putative IE and early promoters, showed no clear evidence of autoregulation, and did not directly inhibit the ORF62 promoter as had been reported previously. ORF63's behavior in transient assays suggests that it plays only a limited regulatory role in modulating VZV gene expression.

Base Sequence↗
PubMed1995

Expression of the herpes simplex virus type 2 latency-associated transcript enhances spontaneous reactivation of genital herpes in latently infected guinea pigs.

The latency-associated transcript (LAT) is the only herpes simplex virus (HSV) gene product detectable in latently infected humans and animals. In this report, we show that a 624-bp deletion in the promoter of the HSV-2 LAT had no discernable effect on viral growth in tissue culture or in acute genital infection of guinea pigs, but impaired LAT accumulation and led to a marked decrease in spontaneous genital recurrences when compared with the behavior of wild-type and rescuant strains. Differences in the ability of the mutant to replicate, or in how readily it established or maintained latency did not account for this finding. Thus, HSV LAT expression facilitates the spontaneous reactivation of latent virus.

Acute Disease↗
PubMed1995

Guidelines for the prevention and treatment of B-virus infections in exposed persons. The B virus Working Group.

Cercopithecine herpesvirus 1 (B virus), enzootic among monkeys of the genus Macaca, causes minimal morbidity in its natural host. In contrast, human B-virus infection presents as rapidly ascending encephalomyelitis with a fatality rate of approximately 70%. This infection remains an uncommon result of macaque-related injuries, although the increase in the use of macaques for research on simian retrovirus infection and hepatitis has expanded the number of opportunities for human exposure. In response to this situation, Emory University and the Centers for Disease Control and Prevention jointly sponsored a B Virus Working Group to formulate a rational approach to the detection and management of human B-virus infection. The resulting guidelines are presented herein and are based upon information from published cases, unpublished cases managed by working-group members, knowledge of the behavior of herpes simplex virus, and--in the absence of hard data--the collective judgment of the group. Although consensus among the co-authors existed on the major points covered by these guidelines, opinions varied widely regarding specific recommendations.

Animals↗
PubMed1995

A controlled seroprevalence survey of primate handlers for evidence of asymptomatic herpes B virus infection.

Herpes B virus (BV) is a common cause of recurring mucocutaneous infections in monkeys of the genus Macaca. Like its human counterpart, herpes simplex virus (HSV), BV establishes lifelong latency and can be reactivated from infected monkeys symptomatically or asymptomatically. Incidental infection of humans handling BV-shedding monkeys can result in fatal meningoencephalitis. To determine whether humans exposed to infected monkeys can acquire asymptomatic BV infections, 480 subjects were evaluated in a controlled seroprevalence study. Sera from 321 primate handlers, including many with repeated injuries inflicted by Macaca monkeys, and 159 people never exposed to monkeys were tested in blinded fashion by both competition ELISA and Western blot to determine the prevalence of BV and HSV seropositivity. Although 293 persons proved positive for HSV antibodies, no primate handlers or control subjects showed BV-specific antibody responses. There is no serologic evidence that BV causes asymptomatic infections in humans.

Adult↗
PubMed1995

Herpes simplex virus trans-regulatory protein ICP27 stabilizes and binds to 3' ends of labile mRNA.

Previous work demonstrated that a herpes simplex virus type 1 (HSV-1) immediate-early function up-regulates beta interferon but not chloramphenicol acetyltransferase reporter genes driven by the strong simian virus 40 (SV40) or cytomegalovirus promoter-enhancer regions in both transient assays and stable cell lines. The different 3' mRNA stabilization and RNA-processing signals from these two reporter genes appeared to be primarily responsible for this phenomenon. We now report that the HSV-1 ICP27 itself is sufficient to stimulate both steady-state accumulation and increased half-life of beta interferon reporter gene mRNA. Furthermore, the ability to respond directly to cotransfected ICP27 can be transferred to chloramphenicol acetyltransferase reporter genes by replacement of their SV40-derived splicing and poly(A) signals with the 3' AU-rich and poly(A) RNA-processing signals from the normally highly labile beta interferon and c-myc mRNA species. ICP27 expressed in bacteria bound specifically to in vitro-generated RNA from both the beta interferon and c-myc intronless AU-rich 3' RNA-processing regions, but not to the SV40-derived early-region splice signal and poly(A) sequences. By site-specific mutagenesis, we also show that individual ICP27 C-terminal amino acid residues that are positionally conserved in ICP27 homologs in other herpesviruses (D-357, E-358, H-479, C-400, C-483, and C-488) are critical for trans-regulatory activity. Importantly, several of these positions match mutations that are known to be essential for the role of ICP27 in the early-to-late switch during the virus lytic cycle. Therefore, our findings support the notion that HSV ICP27 modulates gene expression posttranscriptionally in part by targeting RNA.

Amino Acid Sequence↗