Biomedical subjects

S E Straus

Publications and source records attributed to S E Straus.

At least 145 records · Page 8Linked to original sources

PubMed1993

Studies of herpesvirus infection in chronic fatigue syndrome.

The relationship of herpesviruses to chronic fatigue syndrome has received considerable attention over the past decade. Data suggesting an association fall into three major categories. First, among acute precipitants of the syndrome are primary infections with some herpesviruses, most notably Epstein-Barr virus and cytomegalovirus. Second, a series of studies have detailed elevations of antibodies to most herpesviruses in selected chronic fatigue syndrome populations, with Epstein-Barr virus and human herpes type 6 being the objects of most scrutiny. Third, one recent study reported a greater ease of recovery of human herpes virus type 6 from chronic fatigue syndrome patients. This review article critically examines the cumulative data regarding an association between one or more herpesviruses and the chronic fatigue syndrome in the context of the known biology and epidemiology of these agents. In view of these, and additional considerations regarding study methodologies, the conclusion is drawn that herpesviruses are not dominant causes of the chronic fatigue syndrome and may not even be necessary to the perpetuation of the illness, but it is premature to dismiss entirely this latter possibility.

Cytomegalovirus↗

PubMed1993

HSV-1 activation of HIV-1 transcription is augmented by a cellular protein that binds near the initiator element.

A cellular DNA binding protein, which we term Leader Binding Protein-2 (LBP-2), binds near the transcriptional initiation site of the human immunodeficiency virus type 1 (HIV-1) promoter. This protein recognizes a motif similar to that of LBP-1, a putative repressor of transcription (Kato, H., et al., Science, 251, 1476-1479, 1991). LBP-2 is associated with transcriptional activation of HIV-1 by herpes simplex virus type 1 (HSV-1). Electrophoretic mobility shift assays showed that nuclear levels of this protein increase markedly following HSV-1 infection. Mutations of the LBP binding motif eliminate LBP-2 binding and interfere with HIV-1 activation by HSV-1. When inserted into an unrelated promoter, this motif confers transcriptional responsiveness to HSV-1 infection. Proteins that bind near the initiator element may be important regulators of HIV-1 gene expression.

Base Sequence↗

PubMed1993

Varicella-zoster virus transcription in human trigeminal ganglia.

Our laboratory previously reported in situ hybridization analyses showing varicella-zoster virus (VZV)-specific RNA transcripts in latently infected human trigeminal ganglia. These transcripts were found exclusively in non-neuronal cells and emanated from at least three separate regions of the VZV genome, those encompassing restriction fragments BamHI-EY, EcoRI-B, and BamHI-J. Extending these in situ studies, we now report that VZV RNAs colinear with open reading frames (ORFs) 29 and 62 are demonstrable in non-neuronal cells; however, neither VZV RNA colinear with ORF 28 nor antisense RNAs of ORFs 29 and 62 are detected. Northern hybridization analyses of poly(A)+ RNA from human trigeminal ganglion pools also reveal VZV-specific transcripts corresponding to ORFs 29 and 62, but not those of ORFs 28 or 61. The ORF 29- and 62-specific transcripts are similar to those expressed in productive infection, with regard to size and polyadenylation. The cumulative findings suggest that VZV latency is characterized by selected expression of multiple genes, which appear to include some but not all putative immediate-early and early genes.

Adult↗

PubMed1993

Lymphocyte phenotype and function in the chronic fatigue syndrome.

Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function. Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry. Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced. The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58). CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B. Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities. These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions. This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

Adolescent↗

PubMed1993

Induction and enhancement of immune responses to herpes simplex virus type 2 in humans by use of a recombinant glycoprotein D vaccine.

A vaccine for a chronic or recurrent viral infection should induce immune responses that protect against primary disease or that augment preexisting defenses sufficiently to diminish the likelihood of disease recurrence or progression. Such a vaccine was sought for genital herpes, a sexually transmitted infection of epidemic proportion. Vaccine containing recombinant herpes simplex virus type 2 glycoprotein D expressed in CHO cells was given repeatedly and safely to 24 human volunteers. In previously uninfected subjects, the vaccine induced primary antigen-specific and neutralizing antibody responses nearing or exceeding those seen at entry in subjects with genital herpes. Primary cellular immune responses were also evoked. Vaccination of previously seropositive subjects boosted antibody titers to levels that remained, for > or = 1 year, severalfold above those attained in recurrent genital herpes. Either the quantity or mode of presentation of antigen permitted this vaccine to exhibit previously unachieved immunogenicity, which may prove adequate for antiviral immunoprophylaxis or treatment of genital herpes.

Adult↗

PubMed1993

Varicella-zoster virus DNA polymerase and major DNA-binding protein genes have overlapping divergent promoters.

A detailed analysis of the transcriptionally divergent promoters of varicella-zoster virus (VZV) open reading frames (ORFs) 28 and 29, encoding the DNA polymerase and major DNA-binding proteins, respectively, was performed. We found that the 221-bp ORF 28-29 intergenic domain contains overlapping divergent promoters; these promoters have TATA boxes and cap sites arranged closely back-to-back, have highly concordant patterns of responsiveness to transactivation by VZV ORFs 4 and/or 62, and could not be separated without abolishing the effects that VZV trans activators imparted to them. Mutation of the ORF 28 TATA box rendered this promoter unresponsive to ORF 62 and the combination of ORFs 4 and 62 without altering ORF 29 promoter activity. Mutations of all potential ORF 29 TATA boxes collectively failed to abolish this promoter's responsiveness to either ORF 4 or ORF 62, suggesting a mechanism of gene regulation for ORF 29 that differs from that of ORF 28. These findings are concordant with the observation that both genes are expressed in productive infection, but only ORF 29 expression has been identified in latency.

Animals↗

PubMed1993

Varicella-zoster virus open reading frame 10 protein, the herpes simplex virus VP16 homolog, transactivates herpesvirus immediate-early gene promoters.

The varicella-zoster virus (VZV) open reading frame 10 (ORF10) protein is the homolog of the herpes simplex virus type 1 (HSV-1) protein VP16. These are two virion tegument proteins that have extensive amino acid sequence identity in their amino-terminal and middle domains. ORF10, however, lacks the acidic carboxy terminus which is critical for transactivation by VP16. Earlier studies showed that VZV ORF10 does not form a tertiary complex with the TAATGARAT regulatory element (where R is a purine) with which HSV-1 VP16 interacts, suggesting that ORF10 may not have transactivating ability. Using transient-expression assays, we show that VZV ORF10 is able to transactivate VZV immediate-early (IE) gene (ORF62) and HSV-1 IE gene (ICP4 and ICP0) promoters. Furthermore, cell lines stably expressing ORF10 complement the HSV-1 mutant in1814, which lacks the transactivating function of VP16, and enhance the de novo synthesis of infectious virus following transfection of HSV-1 virion DNA. These results indicate that ORF10, like its HSV-1 homolog VP16, is a transactivating protein despite the absence of sequences similar to the VP16 carboxy-terminal domain. The transactivating function of the VZV ORF10 tegument protein may be critical for efficient initiation of viral infection.

Amino Acid Sequence↗

PubMed1993

Varicella-zoster virus (VZV) open reading frame 61 protein transactivates VZV gene promoters and enhances the infectivity of VZV DNA.

The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is the homolog of herpes simplex virus type 1 (HSV-1) ICP0. Both genes are located in similar parts of the genome, their predicted products share a cysteine-rich motif, and cell lines expressing VZV ORF61 are able to complement an HSV-1 ICP0 deletion mutant (H. Moriuchi, M. Moriuchi, H. A. Smith, S. E. Straus, and J. I. Cohen, J. Virol. 66:7303-7308, 1992). In transient expression assays, HSV-1 ICP0 is a transactivator alone and transactivates in synergy with another viral transactivator, ICP4. However, VZV ORF61 represses the activation by VZV-encoded proteins ORF62 (the homolog of ICP4) and ORF4. To further characterize the function of VZV ORF61 and its role(s) in regulation of viral gene expression, we performed transient expression assays using target promoters from VZV, HSV-1, and unrelated viruses. In the absence of other viral activators, VZV ORF61 transactivated most promoters tested. In addition, a cell line stably expressing VZV ORF61 complemented the HSV-1 mutant in 1814, which lacks the transactivating function of VP16. The cell line expressing VZV ORF61 enhanced the infectivity of HSV-1 virion DNA. Moreover, transient expression of VZV ORF61 also enhanced the infectivity of VZV DNA. These results indicate that VZV ORF61 can stimulate expression of HSV-1 and VZV genes at an early stage in the viral replicative cycle and that ORF61 has an important role in VZV gene regulation.

Animals↗

PubMed1993

A major transactivator of varicella-zoster virus, the immediate-early protein IE62, contains a potent N-terminal activation domain.

Accumulating evidence indicates that the product of the putative immediate-early gene ORF62 (IE62) activates varicella-zoster virus (VZV) genes thought to represent all three kinetic classes, namely, immediate-early (alpha), early (beta), and late (gamma) classes, of VZV genes as well as a variety heterologous gene promoters. However, the mechanism(s) by which IE62 protein mediates transactivation of these diverse VZV and heterologous gene promoters remains to be elucidated. In this study, by using yeast GAL4 protein chimeras, the coding regions of VZV ORF62 possessing activation domains have been assessed. We demonstrate that the VZV IE62 protein contains a potent activation domain in the N-terminal portion of the molecule, encoded within the first 86 codons of ORF62. The predicted secondary structure profile and the acid-base composition of this IE62 domain resemble those of other transregulatory proteins whose activation is mediated through acidic, hydrophobic elements. In addition, we show that deletion of this activation domain from the 1,310-residue native IE62 protein results in ablation of the transactivator function of IE62. We also present evidence that the mutant IE62 protein lacking the activation domain, though devoid of transactivation ability, was still capable of interfering with the activation of target promoters by the native, full-length IE62.

Amino Acid Sequence↗

PubMed1993

Analysis of neuropsychological functioning in patients with chronic fatigue syndrome.

Memory impairment dominates the cognitive complaints of patients with chronic fatigue syndrome (CFS). Twenty CFS patients were available for studies with a clinical and experimental battery composed of memory and cognitive tests. The results on objective testing indicated that the CFS patients had some mild memory impairment, but only on tasks requiring conceptually driven encoding and retrieval processes. There were no associations between the nature of the precipitating illness, self ratings of fatigue, physical findings, or laboratory determination and objective memory performance or self report of memory functioning. These generally negative results indicate that memory impairment in CFS patients is typically mild and involves memory processes that participate in conceptualising information.

Adult↗

PubMed1993

Herpes simplex virus type 1 transcription is not detectable in quiescent human stromal keratitis by in situ hybridization.

PURPOSE: The purpose of this study was to determine whether herpes simplex virus (HSV) transcripts are present in the corneas of patients with chronic herpetic stromal keratitis. METHODS: Corneal buttons from patients with a history of stromal keratitis, but no ongoing active disease, together with positive and negative control tissues, were analyzed by in situ hybridization using single-stranded RNA probes for all three classes of viral lytic cycle transcripts as well as for the latency-associated transcripts (LATs). Tissues also were screened for presence of HSV genomic DNA using the polymerase chain reaction (PCR). RESULTS: HSV DNA was detected in 7 of 13 quiescent corneas by PCR, but no viral transcripts were detected in any of these corneas by in situ hybridization. CONCLUSIONS: At the level of detection afforded by in situ hybridization, HSV persistent in scarred human corneas after stromal keratitis appears to be transcriptionally dormant. This contrasts with the situation in neurons of latently infected sensory ganglia, in which LATs are present at high levels.

Animals↗

PubMed1992

Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings.

The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness "chronic fatigue syndrome." Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity.

Adult↗

PubMed1992

NIH conference. Chronic fatigue syndrome research. Definition and medical outcome assessment.

A workshop was held 18 to 19 March 1991 at the National Institutes of Health to address critical issues in research concerning the chronic fatigue syndrome (CFS). Case definition, confounding diagnoses, and medical outcome assessment by laboratory and other means were considered from the perspectives of key medical specialties involved in CFS research. It was recommended that published Centers for Disease Control (CDC) case-definition criteria be modified to exclude fewer patients from analysis because of a history of psychiatric disorder. Specific recommendations were made concerning the inclusion or exclusion of other major confounding diagnoses, and a standard panel of laboratory tests was specified for initial patient evaluation. The workshop emphasized the importance of recognizing other conditions that could explain the patient's symptoms and that may be treatable. It was viewed as essential for the investigator to screen for psychiatric disorder using a combination of self-report instruments followed by at least one structured interview to identify patients who should be excluded from studies or considered as a separate subgroup in data analysis. Because CFS is not a homogeneous abnormality and because there is no single pathogenic mechanism, research progress may depend upon delineation of these and other patient subgroups for separate data analysis. Despite preliminary data, no physical finding or laboratory test was deemed confirmatory of the diagnosis of CFS. For assessment of clinical status, investigators must rely on the use of standardized instruments for patient self-reporting of fatigue, mood disturbance, functional status, sleep disorder, global well-being, and pain. Further research is needed to develop better instruments for quantifying these domains in patients with CFS.

Centers for Disease Control and Prevention, U.S.↗

PubMed1992

Transactivation of the HIV-1 LTR by HSV-1 immediate-early genes.

Herpes simplex virus type 1 (HSV-1) activates transcription from the long terminal repeat (LTR) promoter region of the human immunodeficiency virus type 1 (HIV-1). HSV-1 immediate-early (IE) genes ICP0 and ICP4 are thought to be important mediators of this process, which is known to involve the induction of the cellular activators NF-kappa B and Sp1. We demonstrate that ICP0 and ICP4 transactivation of the LTR is largely dependent on the presence of NF-kappa B and Sp1 binding sites. However, in Jurkat CD4-positive lymphocytes, HSV-1 activates LTR constructs lacking all NF-kappa B or Sp1 Binding sequences. This effect is still evident when all sequences upstream of the TATA motif are removed. Such enhancer-independent transactivation can be produced by cotransfection of ICP0 and ICP4. Thus HSV-1 IE genes transactivate the HIV-1 LTR both through the induction of NF-kappa B and Sp1 and through another as yet undefined cellular factor.

Animals↗

PubMed1992

UV light-induced reactivation of herpes simplex virus type 2 and prevention by acyclovir.

UV B light is a potent stimulus for inducing reactivation of latent herpes simplex virus (HSV) infections. Patients were enrolled in a double-blind placebo-controlled crossover trial to determine whether acyclovir can prevent UV light-induced HSV-2 recurrences. Twenty-four patients with a history of recurrent infection of perigenital sites (e.g., buttock, thigh) were exposed one to four times with 4 minimum erythema doses of UV light. Patients were given acyclovir 200 mg orally five times daily or matched placebo beginning 1 day before each exposure and continuing for 5 days after exposure. There were 13 UV-induced recurrences among 36 placebo treatments and 3 after 38 acyclovir treatments (P = .004). The mean time to recurrence (+/- SE) was 4.8 +/- 0.3 days. HSV-2 lesions developed primarily at the site of UV exposure. The cutaneous distribution and timing of UV-induced recurrences was consistent with a neural localization (dorsal root ganglia) of latent viral infection. This UV light model permits direct examination of events leading to HSV-2 recurrences in humans and can be used to evaluate approaches to prevention.

Acyclovir↗

PubMed1992

Comparative biology of latent varicella-zoster virus and herpes simplex virus infections.

The clinicoepidemiologic features of varicella-zoster virus and herpes simplex virus latency are clearly distinctive. These differences indicate that each virus has evolved a unique strategy to ensure the establishment and maintenance of latency and to reactive therefrom. Indeed, current data reveal divergent pathogenetic and molecular biologic properties that may account for the clinicoepidemiologic characteristics that distinguish recurrent infections with these herpesviruses.

Aging↗

PubMed1992

Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0.

The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is thought to be the homolog of herpes simplex virus type 1 (HSV-1) ICP0, based on gene location and limited amino acid homology. However, HSV-1 ICP0 trans activates HSV-1 genes, while VZV ORF61 protein trans represses the function of VZV trans activators on VZV promoters in transient expression assays. To investigate the functional relatedness of HSV-1 ICP0 and VZV ORF61 protein, we established Vero and MeWo cell lines which stably express VZV ORF61 under the control of a metallothionein promoter and performed complementation studies with an HSV-1 ICP0 deletion mutant (7134). Mutant 7134 is impaired for plaque formation and replication at a low multiplicity of infection in cell culture, but these defects were complemented by up to 200-fold in Vero cell lines expressing VZV ORF61. Likewise, the efficiency of plaque formation was improved by up to 100-fold in MeWo cell lines expressing VZV ORF61. A cell line expressing another VZV immediate-early gene product (ORF62) was unable to complement mutant 7134. HSV-1 mutants which are deleted for other HSV-1 immediate-early gene products (ICP4, ICP27) were unable to grow in VZV ORF61-expressing cell lines. These results indicate that, despite marked differences in their sequences and in effects on their cognate promoters in transient expression assays, VZV ORF61 protein is the functional homolog of HSV-1 ICP0.

Amino Acid Sequence↗

PubMed1992

Acute progressive Epstein-Barr virus infections.

A few Epstein-Barr virus (EBV) infections result in progressive, potentially fatal disease. Nearly all of these progressive EBV infections occur in individuals known or suspected to be immunodeficient. Diagnosis and treatment are difficult.

Herpesviridae Infections↗