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T Bergström

Publications and source records attributed to T Bergström.

At least 37 records · Page 2Linked to original sources
PubMed1999

Successful treatment of generalized primary herpes simplex type 2 infection during pregnancy.

Generalized herpes simplex virus infections constitute a severe threat to mother and child during pregnancy. Before antiviral treatments were available, both mother and foetus had a high mortality rate. The following case illustrates a successful outcome after long-term antiviral treatment. It is of great importance to suspect, diagnose and treat patients with HSV 2 early, especially during pregnancy.

Acyclovir↗
PubMed1999

The role of a single N-linked glycosylation site for a functional epitope of herpes simplex virus type 1 envelope glycoprotein gC.

A monoclonal antibody, B1C1, binding to an epitope of antigenic site II of the herpes simplex virus type 1 (HSV-1) glycoprotein gC-1, is a potent inhibitor of two important biological functions of gC-1: its binding to cell surface heparan sulfate and its binding to the receptor for complement factor C3b. Here, we have analyzed a B1C1-resistant HSV-1 variant (HSV-12762/B1C1B4.2), obtained after passage of wild type HSV-1 (HSV-12762) in the presence of high concentrations of B1C1. The transport of newly synthesized mutant gC-1 to the cell surface was comparable to that of wild type glycoprotein, but no binding of surface-associated mutant gC-1 to B1C1 was detected. However, mutant and wild type gC-1 bound equally well to other site II Mabs. Attachment of wild type but not mutant virus was inhibited by B1C1. Sequencing of the mutant gC-1 gene revealed only one nucleotide change, resulting in replacement of Thr150 by an Ile, in turn destroying an N-glycosylation site at Asn148. Loss of one complex type N-linked glycan was confirmed by endoglycosidase digestion and subsequent SDS-polyacrylamide gel electrophoresis. Circular dichroism analysis of purified gC-1 from cells infected with mutant or wild type virus did not reveal any difference in secondary structure between mutant and wild type gC-1. It was not possible to obtain a B1C1-resistant phenotype by nucleotide-directed mutagenesis of gC-1 where Asn148 was changed to a glutamine. These data demonstrated that the threonine of the glycosylation site and not the N-linked glycan in itself was essential for B1C1 binding

Amino Acid Sequence↗
PubMed1999

Variability of the glycoprotein G gene in clinical isolates of herpes simplex virus type 1.

Glycoprotein G (gG) of herpes simplex virus type 1 (HSV-1) has been used as a prototype antigen for HSV-1 type-specific serodiagnosis, but data on the sequence variability of the gene coding for this protein in wild-type strains are lacking. In this study, direct DNA sequencing of the gG-1 genes from PCR products was performed with clinical HSV-1 isolates from 11 subjects as well as with strains Syn 17(+), F, and KOS 321. The reference strains Syn 17(+) and F showed a high degree of conservation, while KOS 321 carried 13 missense mutations and, in addition, 12 silent mutations. Three clinical isolates showed mutations leading to amino acid alterations: one had a mutation of K(122) to N, which is a gG-1-to-gG-2 alteration; another contained all mutations which were observed in KOS 321 except two silent mutations; and the third isolate carried five missense mutations. Two clinical isolates as well as strain KOS 321 showed a mutation (F(111)-->V) within the epitope of a gG-1-reactive monoclonal antibody (MAb). When all viruses were tested for reactivity with the anti-gG-1 MAb, the three strains with the F(111)-->V mutation were found to be unreactive. Furthermore, gG-1 antibodies purified from sera from the two patients carrying strains mutated in this epitope were less reactive when they were tested by an HSV-1-infected-cell assay. Therefore, our finding that the sequence variability of the gG-1 gene also affects B-cell epitope regions of this protein in clinical isolates may have consequences for the use of this protein as a type-specific antigen for serodiagnosis.

Adult↗
PubMed1999

Typing of clinical herpes simplex virus type 1 and type 2 isolates with monoclonal antibodies.

The purpose of this study was to evaluate the performance of a herpes simplex virus (HSV) type 1-specific anti-glycoprotein C-1 monoclonal antibody (MAb) and a type 2-specific anti-glycoprotein G-2 MAb for typing of 2,400 clinical HSV-1 isolates and 2,400 clinical HSV-2 isolates, respectively, using an enzyme immunoassay. The anti-HSV-1 MAb showed sensitivity and specificity of 100%, and the anti-HSV-2 MAb showed a sensitivity of 99.46% and 100% specificity, indicating that these MAbs are suitable for typing of clinical HSV isolates.

Antibodies, Monoclonal↗
PubMed1999

Herpes simplex virus type 2 glycoprotein G-negative clinical isolates are generated by single frameshift mutations.

Herpes simplex virus (HSV) codes for several envelope glycoproteins, including glycoprotein G-2 (gG-2) of HSV type 2 (HSV-2), which are dispensable for replication in cell culture. However, clinical isolates which are deficient in such proteins occur rarely. We describe here five clinical HSV-2 isolates which were found to be unreactive to a panel of anti-gG-2 monoclonal antibodies and therefore considered phenotypically gG-2 negative. These isolates were further examined for expression of the secreted amino-terminal and cell-associated carboxy-terminal portions of gG-2 by immunoblotting and radioimmunoprecipitation. The gG-2 gene was completely inactivated in four isolates, with no expression of the two protein products. For one isolate a normally produced secreted portion and a truncated carboxy-terminal portion of gG-2 were detected in virus-infected cell medium. Sequencing of the complete gG-2 gene identified a single insertion or deletion of guanine or cytosine nucleotides in all five strains, resulting in a premature termination codon. The frameshift mutations were localized within runs of five or more guanine or cytosine nucleotides and were dispersed throughout the gene. For the isolate for which a partially inactivated gG-2 gene was detected, the frameshift mutation was localized upstream of but adjacent to the nucleotides coding for the transmembranous region. Thus, this study demonstrates the existence of clinical HSV-2 isolates which do not express an envelope glycoprotein and identifies the underlying molecular mechanism to be a single frameshift mutation.

Amino Acid Sequence↗
PubMed1999

PCR detection of Epstein-Barr virus, herpes simplex virus and human papillomavirus from the anal mucosa in HIV-seropositive and HIV-seronegative homosexual men.

This study aimed to examine the prevalence of the Epstein-Barr virus (EBV), herpes simplex virus (HSV) and human papillomavirus (HPV) in the anal and oral mucosa of homosexual men with and without HIV infection and to correlate these findings to CD4+ count and anal cytology. Anal and oral cell samples from 20 HIV-infected and 14 non-infected homosexual men attending the STD clinic at Sahlgrenska University Hospital, Goteborg were examined for EBV, HSV and HPV by the polymerase chain reaction (PCR) technique. Proctoscopy was performed in all patients and swabs for cytology were taken. EBV was demonstrated in 32% (6/19) of anal cell samples from the HIV-positive group but in none from 13 HIV-negative men. Asymptomatic shedding of HSV type 2 from the anus was detected in 3 of 19 HIV-positive men, all with low CD4+ counts and abnormal cytology. No patient in the HIV-negative group shed HSV from the anus. HPV was demonstrated in 16 of 17 anal cell samples in the HIV-infected group and in 7 of 13 HIV-negative men. More than one HPV type was detected in 7 HIV-infected men. Five (29%) of 17 HIV-positive patients exhibited abnormal cytology whereas none did so in the HIV-negative group. Those with abnormal cytology all had CD4+ counts below 0.35 and were infected with multiple HPV types including HPV 16/18. In conclusion, our results demonstrate an enhanced expression of HPV as well as EBV from the anus in HTV-infected homosexual men. In this small number of patients EBV was not related to low CD4+ count or to abnormal cytology.

AIDS-Related Opportunistic Infections↗
PubMed1998

Interaction between pseudorabies virus and heparin/heparan sulfate. Pseudorabies virus mutants differ in their interaction with heparin/heparan sulfate when altered for specific glycoprotein C heparin-binding domain.

Cell surface heparan sulfate serves as an initial receptor for a number of herpesviruses including pseudorabies virus (PrV). It has been demonstrated that the heparan sulfate-binding domain of PrV glycoprotein C is composed of three discrete clusters of basic residues corresponding to amino acids 76-RRKPPR-81, 96-HGRKR-100, and 133-RFYRRGRFR-141, respectively, and that these clusters are functionally redundant, i.e. each of them could independently support PrV attachment to cells (Flynn, S. J., and Ryan, P. (1996) J. Virol. 70, 1355-1364). To evaluate the functional significance of each of these clusters we have used PrV mutants in which, owing to specific alterations in glycoprotein C, the heparan sulfate-binding site is dominated by a single specific cluster. These mutants exhibited different patterns of susceptibility to selectively N-, 2-O-, and 6-O-desulfated heparin preparations in virus attachment/infectivity assay. Moreover PrV mutants differed as regard to efficiency of their attachment to and infection of cells pretreated with relatively low amounts of heparan sulfate-degrading enzymes. Furthermore glycoprotein C species, purified from respective mutants, bound heparin oligosaccharide fragments of different minimum size. These differences suggest that specific clusters of basic amino acids of the heparan sulfate-binding domain of glycoprotein C may support PrV binding to different structural features/stretches within the heparan sulfate chain.

Amino Acid Sequence↗
PubMed1998

Acute viral encephalitis in adults--a prospective study.

We have prospectively studied 27 adult patients attending the Department of Infectious Diseases, Göteborg, Sweden, between October 1992 and October 1996 with a diagnosis of acute viral encephalitis. In addition to cerebrospinal fluid (CSF) virus isolations and antibody analyses against herpes simplex virus, cytomegalovirus, varicella zoster virus, Epstein-Barr virus (EBV), enterovirus, adenovirus, tick-borne encephalitis virus, and mycoplasma, polymerase chain reaction test (PCR) to 5 viruses from the family of human herpes viridae, and to adenovirus as well as to enterovirus were analysed in CSF. 10 patients had herpes simplex virus type-1 (HSV-1), 1 had varicella zoster virus, 1 had tick-borne encephalitis, and 2 had Influenza A infections. In 13 patients the aetiology remained unclear. Eight patients with HSV-1 encephalitis and clinical symptoms for 2-11 d before admission were PCR-positive, while 2 patients with a < or = 2 d history of disease were negative for HSV-1 DNA on admission. These 2 patients became positive for HSV-1 DNA in CSF samples taken 4 d later in 1 case and 7 d later in the other. In 4 patients with HSV-1 encephalitis, in 1 patient with Influenza A complicated by encephalitis, and in 1 patient with encephalitis of unknown origin EBV DNA was found in CSF samples during the study. The clinical significance of these findings is unclear. The study shows that HSV-1 was the most common etiological agent in patients with viral encephalitis in the Göteborg area. In spite of improved diagnostic procedures, a large proportion of patients with symptoms and laboratory findings compatible with viral encephalitis still have an unclear aetiology.

Acute Disease↗
PubMed1998

Congenital toxoplasma gondii infection diagnosed by PCR amplification of peripheral mononuclear blood cells from a child and mother.

A case of congenital toxoplasmosis is presented, where diagnosis by PCR amplification of Toxoplasma gondii DNA from peripheral blood led to early treatment of the infant and seemingly normal brain development despite the presence of intracranial calcifications at birth. The mother, who experienced a subclinical infection during pregnancy, was PCR-positive for toxoplasma DNA in a sample of peripheral blood drawn after delivery.

Animals↗
PubMed1998

Tumor necrosis factor-alpha response and herpesvirus infection in Bell's palsy.

OBJECTIVES: To attempt early diagnosis of patients with Bell's palsy by detection of herpesviral DNA in body fluids, and to investigate whether tumor necrosis factor-alpha (TNF-alpha), a cytokine associated with demyelination, is involved in the inflammatory response in this disease. STUDY DESIGN: Eleven patients with acute facial palsy admitted within 1 week after onset of the disease were followed in a consecutive prospective study. METHODS: Antibodies reactive to herpesviruses were determined by enzyme-linked immunosorbent assay in serum samples from acute and convalescent (> 2-week interval) cases. Intrathecal antibody response was investigated by immunoblotting. Polymerase chain reaction amplification of herpesviral DNA was attempted from samples of serum, cerebrospinal fluid, tear fluid, and saliva TNF-alpha and its soluble receptors (types I and II) were assessed in serum and cerebrospinal fluid samples. RESULTS: Ten of the 11 patients demonstrated serologic evidence of herpesviral primary infection or reactivation, supporting the evidence that herpesviruses are the most prevalent etiologic agents in Bell's palsy. Despite this, DNA amplifications by polymerase chain reaction were negative for herpesviruses in the body fluids tested. TNF-alpha concentrations were significantly elevated in serum, as compared with controls. Only one patient had a remaining facial nerve dysfunction at follow-up after 3 months. CONCLUSION: The absence of herpes DNA in body fluids in the acute stage of serologically confirmed Bell's palsy suggests that viral replication is transient in cases with an early restoration of the facial nerve function. The elevated serum levels of TNF-alpha indicate that this cytokine might be a pathogenetic factor related to the demyelination in this disease.

Adult↗
PubMed1998

Localization of type-specific epitopes of herpes simplex virus type 2 glycoprotein G recognized by human and mouse antibodies.

Glycoprotein G is a major target for the humoral immune response against herpes simplex virus (HSV) and a prototype antigen for type-specific serodiagnosis discriminating HSV-1 and HSV-2 infections. The mature part of HSV-2 glycoprotein G-2 (gG-2) contains a unique stretch suspected to mediate type specificity, and in addition a region homologous to HSV-1 glycoprotein G-1 (gG-1). Antigenic determinants of the mature gG-2 were mapped by testing the reactivity of mouse anti-gG-2 monoclonal antibodies (MAbs) and purified human anti-gG-2 antibodies with synthetic peptides coupled to cellulose membranes. The anti-gG-2 MAbs bound to four epitopes localized in a narrow cluster within a gG-2 segment delimited by amino acids (aa) 552 and 611. This cluster was located between the predicted O-glycan-rich region and the transmembrane anchor sequence. The epitopes of the human anti-gG-2 antibodies were localized within three stretches of amino acids, two of which were overlapping with those recognized by anti-gG-2 MAbs. One of these stretches, delimited by aa 552 and 574, showed reactivity to all human HSV-2 sera tested, but not to HSV-1 sera or to purified anti-gG-1 antibodies. Neither the anti-gG-2 MAbs nor the purified human anti-gG-2 antibodies were cross-reactive to gG-1 peptides or HSV-1 antigen, although most of the epitopes were localized within the part of gG-2 which was homologous to gG-1. The findings concerning HSV-2 type-specific human antibody response to a defined stretch within gG-2 may be of importance for the further development of type-discriminating serodiagnosis.

Amino Acid Sequence↗
PubMed1997

Structural requirement of heparan sulfate for interaction with herpes simplex virus type 1 virions and isolated glycoprotein C.

Cell surface heparan sulfates mediate primary attachment of herpes simplex virus type 1, the first step in virus invasion of the cells. Removal of the host cell heparan sulfate results in a significantly diminished susceptibility of the cell to virus infection. On the virus envelope, glycoprotein C has been identified as the major binding site for heparan sulfate in the primary attachment of the virus to host cells. Using selectively desulfated heparins and metabolically labeled host cell heparan sulfate, we have analyzed the structural requirements of heparan sulfate to provide binding sites for glycoprotein C and the whole virus. Employing glycoprotein C affinity chromatography and a virus binding assay, we subfractionated oligosaccharides derived from heparan sulfate and partially desulfated heparin into selectively bound and unbound pools. These were chemically depolymerized and analyzed at the disaccharide level. The shortest glycoprotein C-binding fragment consisted of 10-12 monosaccharide units containing at least one 2-O- and one 6-O-sulfate group that have to be localized in a sequence-specific way, based on the finding that bound and unbound HS fragments do not differ in charge or composition. The binding sequence is found within N-sulfated blocks of heparan sulfate, although several N-acetyl groups can be tolerated within the minimal binding sequence. These minimal requirements for herpes simplex virus type 1 binding to heparan sulfate are clearly distinct from other identified protein binding sites.

Animals↗
PubMed1997

Relation between polymerase chain reaction findings and morphological changes during cytomegalovirus infection in transplanted lung.

Cytomegalovirus (CMV) can be present as a latent or productive infection resulting in disease. The polymerase chain reaction (PCR) is a sensitive technique to document the presence of CMV (DNA). Negative reactions are indicative of its absence. The presence of CMV (DNA) was assessed longitudinally in 261 transbronchial lung biopsy (TBB) specimens from 37 patients over a 6-month period. The TBB specimens from six serologically CMV-negative recipients who received lungs from serologically CMV-negative donors never showed a positive CMV-PCR(DNA) reaction during the study. Based on a study of their TBB specimens, 10 serologically CMV-positive recipients who received lungs from serologically CMV-negative donors all developed a CMV-PCR(DNA)-positive reaction and five (50%) morphologically manifested CMV disease. The remaining 21 serologically CMV-positive recipients who received lungs from serologically CMV-positive donors all developed a CMV-PCR(DNA)-positive reaction and 15 (71%) developed CMV pneumonitis. The data show that development of a positive CMV-PCR(DNA) reaction in a TBB sample within the first month after transplantation indicates a greatly increased risk of developing CMV disease. In addition, a positive CMV-PCR(DNA) reaction preceded morphologically manifest disease on average by 2 weeks. Comparisons between TBB and bronchoalveolar lavage show the former to provide a more dependable template.

Adolescent↗
PubMed1997

Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis.

Several members of the herpesvirus family have been implicated in the pathogenesis of multiple sclerosis (MS). Recently, HHV-6 viral antigen has been demonstrated in association to MS plaques, as well as DNA from human herpesvirus 6 (HHV-6) in cerebrospinal fluid from a few MS patients by polymerase chain reaction (PCR). In the present study, CSF from patients with MS, optic neuritis and other neurological diseases, as well as consecutive CSF and serum samples from MS patients included in a clinical trial with acyclovir, were analysed by nested PCR for the presence of DNA from herpes simplex virus 1 and 2, Epstein-Barr virus, varicella zoster virus, cytomegalovirus, human herpesvirus 6 and 7. No virus DNA was found in any CSF (n = 115) or serum (n = 116) sample. These findings argue against a continuous disseminated herpesvirus infection in MS, but do not rule out a lesion-associated, low-grade herpesvirus infection within the MS brain.

Adolescent↗
PubMed1997

HLA class II alleles in Amerindian populations: implications for the evolution of HLA polymorphism and the colonization of the Americas.

The analysis of HLA allele frequencies in various Amerindian populations may shed light on the history of human migrations in the Americas; the overall reduction in the number of alleles relative to non-Amerindian populations and the observation that the same alleles and allelic lineages are "missing" in all Amerindian groups suggests an "Into America" population bottleneck. The identification of previously unreported (and presumably newly arisen) HLA-DRB1 alleles among isolated Amerindian groups, (DRB*0417 in Argentina, *08042 in Ecuador, DRB1*0807 in Brazil, and *0811 in Canada) suggests that these alleles may have been generated since the colonization of the Americas (about 20-30,000 years ago). These observations are difficult to reconcile with the notion, based on the analysis of exon-2 sequences, that most of the human DRB1 alleles are "ancient", that is, predate the divergence of the hominoids (4-7 myr). Recent analyses of DRB1 intron sequences, however, indicate that, although most of the allelic lineages are ancient, the alleles within a lineage (> 90% of the DRB1 alleles) have arisen relatively recently. For DRB1*0807, presumably generated by an Asp to Val change (GAT to GTT) at codon 57, strong selective pressures appear to be in operation, based on the high frequency (23%), and linkage disequilibrium patterns of this allele. The analysis of a complex microsatellite in the second intron in the Ticuna is consistent with the notion that the new Amerindian DR8 alleles arose from DRB1*0802, the only DR8 allele observed in most Amerindian populations.

Alleles↗
PubMed1997

Epstein-Barr virus DNA in the uterine cervix of teenage girls.

OBJECTIVES: To: (i) evaluate longitudinally the prevalence of Epstein-Barr virus (EBV) DNA in the cervix of healthy teenage girls, (ii) relate the presence of cervical EBV DNA to virginity or sexual experience, and (iii) relate the occurrence of cervical EBV DNA to the presence of specific IgG antibodies to EBV virus capsid antigen (EBV-VCA) in serum and to signs of genital infection. MATERIAL AND METHODS: Thirty-six teenage girls were followed for 2 years between the ages of 16 and 18 years. A sexual history was taken and a gynecological examination was performed on each occasion. The presence of EBV DNA in the cervix and of EBV VCA antibodies in serum was determined on each occasion. RESULTS: Coitus debut was reported by 23/36 girls (64%) and by 31/36 (86%) at 16- and 18-years of age, respectively. Two girls (only one with sexual debut) harbored EBV DNA in the cervix at 16 years of age. At the age of 18, no EBV DNA was found in these two girls, but another three girls carried EBV DNA in the cervix. All were sexually active and reported 1, 4 and 7 life-time sexual partners respectively. Serum EBV-VCA antibodies were found in 83% of the 16-year old girls and in 89% of the 18-year old girls (no significant difference between sexually experienced and virginal girls at either age). All the girls with cervical EBV DNA had antibodies against EBV-VCA. None of the girls with EBV DNA were found to carry HPV DNA or have a chlamydial infection in the cervix at any time during the study. There was no significant difference in the number of girls with a cervix secretion predominated by leucocytes between girls with positive and negative cervical EBV DNA samples. CONCLUSIONS: We conclude that among these healthy teenage girls the non-sexual route of transmission of EBV is more plausible than the sexual one.

Adolescent↗