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Biomedical subjects

P Goubau

Publications and source records attributed to P Goubau.

At least 19 recordsLinked to original sources

Characteristics of Epstein-Barr virus primary infection in pediatric liver transplant recipients.

BACKGROUND/AIM: Pediatric liver transplant recipients are at high risk of Epstein-Barr virus infection. However the incidence of clinical symptoms and the graft function at the time of acute infection remains poorly documented. The aim of this study was to monitor the clinical and biochemical events associated with primary Epstein-Barr virus infection. METHODS: Clinical and biological patterns associated with Epstein-Barr virus infection were prospectively searched in 38 liver transplanted children. Polymerase chain reaction and anti-Epstein-Barr virus IgM antibodies were used at regular intervals to detect the timing of primary infection. RESULTS: Five children (13%) had pretransplant immunity, 26 (68.5%) developed primary Epstein-Barr virus infection 15 to 90 days after transplantation and seven (18.5%) remained Epstein-Barr virus negative. The four patients with clinical symptoms at the time of infection subsequently developed post-transplant lymphoproliferative disease. A single post-transplant lymphoproliferative disease occurred in non-symptomatic patients (overall incidence 13%). No mortality was associated with post-transplant lymphoproliferative disease. Two asymptomatic patients had abnormal liver function tests possibly related to primary Epstein-Barr virus infection. CONCLUSION: Epstein-Barr virus primary infection occurs in 80% of seronegative patients within 3 months after OLT. Clinical symptoms are rare and closely associated with post-transplant lymphoproliferative disease. Outside post-transplant lymphoproliferative disease, the consequences of infection are marginal.

Adolescent↗

Reactivity to p52 and CM2 recombinant proteins in primary human cytomegalovirus infection with a microparticle agglutination assay.

We evaluated the reactivities of sera against p52 and CM2 recombinant antigens of human cytomegalovirus (HCMV), coated on microparticles, for the differentiation of primary HCMV infection from an established infection. Two different test formats of the CMV Multiplex Copalis assay were evaluated. The 214 serum samples tested were immunoglobulin M (IgM) positive or equivocal by our reference assay. Reactivities against p52 and CM2 antigens were tested for sera from 37 patients with a well-documented seroconversion within the preceding 3 months (119 serum specimens), 31 patients known to have had a seroconversion at least 8 months earlier (31 serum specimens), and 57 patients without a documented seroconversion (64 serum specimens). The assay had a sensitivity for the detection of a primary infection of 70 or 86% by the first test format and a sensitivity of 88 or 94% by the second test format, according to the criteria used to indicate a primary infection by this test. A good correlation of the results of the assay with our in-house avidity index was found. The specificity of the assay warrants further evaluation. With IgM-positive sera, the assay was not sufficiently specific to make a distinction between a primary infection and an established infection.

Agglutination Tests↗

High prevalence of GB virus C/hepatitis G virus in Kinshasa, Democratic Republic of Congo: a phylogenetic analysis.

A prevalence of 10.3% of GB virus C (GBV-C)/hepatitis G virus (HGV) carriers was found in 97 pregnant women from Kinshasa, Congo (formerly Zaire), while prevalences of 1%, 4.1%, and 0% were found for hepatitis C virus, human immunodeficiency virus, and human T-lymphotropic virus respectively. Phylogenetic analysis of the ten GBV-C/HGV positives based on the 5' non-coding region using three different methods identified consistently three GBV-C/HGV genotypes. Four main clades were found within the type 1 sequences. All the Congolese isolates are GBV-C/HGV type 1 in two different clades. The clustering of seven Congolese isolates was inconsistent in different methods. Further likelihood-mapping analysis showed a well-resolved phylogeny, confirming the clustering of the seven Congolese isolates with a Belgian strain representing a new clade in the GBV-C/HGV type 1 sequences.

Deltaretrovirus Infections↗

Influence of CD4+ lymphocyte counts on GB virus C/hepatitis G virus carriership in HIV-positive individuals.

The duration of the GB virus C or hepatitis G virus (GBV-C/HGV) carriership varies according to the patient group studied. The immune competence of the host may be important. GBV-C/ HGV was studied in human immunodeficiency virus (HIV)-infected persons and an attempt was made to correlate the presence of viral RNA or E2 antibodies with CD4+ lymphocyte counts. Of 138 HIV-positive subjects, 30 were GBV-C/HGV RNA-positive and 20 others were E2 antibody-positive, whereas in healthy GBV-C/HGV-infected persons, the proportion of E2 antibody carriers was much higher. On the other hand, a relationship was not found between CD4+ lymphocyte counts and the presence of GBV-C/HGV RNA in the HIV-infected persons. This result does not necessarily imply that the CD4+ lymphocyte count does not affect viral clearance, but the results could be due to the trans-sectional nature of this study. A longitudinal assessment should clarify this point.

CD4 Lymphocyte Count↗

Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection.

Human cytomegalovirus (HCMV) is the most common cause of viral intra-uterine infection. The experience with prenatal diagnosis remains limited and is based on few reports of small numbers of cases. It is thus difficult to compare the accuracy of the different tests because the groups studied were small and heterogeneous. We describe here our experience on a series of 98 pregnancies leading to HCMV congenital infection, among which 71 have been tested by amniotic fluid (AF) sampling followed by culture and/or polymerase chain reaction (PCR). Independently of the delay between AF sampling and the first HCMV IgM positive result, the mean sensitivity of both culture and PCR was around 70 per cent. The best sensitivity (95.5 per cent) was obtained after a delay > or = 6 weeks in late pregnancy (> or = 23 weeks). The present study demonstrated clearly that the delay between AF puncture and the presumed date of seroconversion is more important for sensitivity than the technique used for the diagnosis (PCR or culture). However, even in the best diagnostic conditions, negative results of HCMV culture or PCR in AF cannot formally exclude intra-uterine infection.

Amniocentesis↗

The discovery of two new divergent STLVs has implications for the evolution and epidemiology of HTLVs.

We have isolated and characterised two divergent simian T-lymphotropic viruses (STLV), not belonging to the established human and simian T-lymphotropic virus lineages HTLV-1/STLV-1 and HTLV-2. STLV-L, from an Eritrean sacred baboon (Papio hamadryas), has been typed as a third type of simian T-lymphotropic virus, distinct from HTLV-1/STLV-1 and HTLV-2. The other virus, isolated from Congolese bonobos (Pan paniscus), is a distinct member of the HTLV-2 clade and has been designated STLV-2. The isolation of these two simian viruses shows that the spectrum of HTLVs/STLVs is larger than previously expected. Our data indicate that the two lineages STLV-L and HTLV-2/STLV-2 are of African origin, while the HTLV-1/STLV-1 lineage has been shown to be of Asian origin. These data, together with our phylogenetic analyses, suggest an African origin of the HTLV/STLV ancestor, which provides new clues about virus dissemination. Furthermore, the atypical serological profiles exhibited by STLV-L or STLV-2 infected animals in western blot, raise questions about the efficiency of current screening methods to type highly divergent HTLVs/STLVs. Considering the growing interest in xenotransplantations, more epidemiological and biological knowledge of simian and human T-lymphotropic viruses is necessary to estimate the risk of interspecies transmissions.

Animals↗

Predictive value of maternal-IgG avidity for congenital human cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) is now the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from recurrent or persistent HCMV infection in pregnant females. For this purpose, IgM tests are not reliable enough and the measurement of the IgG avidity appears to be presently the best method. OBJECTIVE: To evaluate the performance of the measurement of HCMV-IgG avidity by a 8 M urea denaturation assay in predicting congenital infection in the offspring. STUDY DESIGN: Seventy-eight women were included in this study on the basis of a HCMV IgM positive or equivocal result on a first serum during pregnancy, but without a documented seroconversion history. The IgG avidity was measured and correlated with the outcome of the pregnancy. RESULTS: In eight cases of HCMV in utero infection the maternal HCMV-IgG avidity index was below 50%. One case of HCMV in utero infection was observed despite a high avidity index during the second trimester of the pregnancy. High or intermediate HCMV-IgG avidity indexes during the first trimester of pregnancy were not associated with a congenital infection. CONCLUSIONS: Even in the presence of an IgM positive result, an HCMV IgG avidity index above 65% on a serum obtained during the first trimester of pregnancy could reasonably be considered as a good indicator of past HCMV infection. In these conditions invasive prenatal diagnosis is not necessary.

Antibodies, Viral↗

Prevalence of GB virus C/hepatitis G virus among blood donors in north-eastern Brazil.

We tested 70 blood donors from Fortaleza (Ceara state, Brazil) for GB virus C/hepatitis G virus (GBV/HGV) infection by polymerase chain reaction and detection of antienvelope antibodies. Twenty-seven (38.6%) showed signs of an active or resolved infection. Sixty-four percent of those with indications of other blood-borne viral infections showed signs of GBV-C/HGV infection also.

Blood Donors↗

Epstein-Barr virus infection in sixty pediatric liver graft recipients: diagnosis of primary infection and virologic follow-up.

BACKGROUND: Epstein-Barr virus (EBV) is an important cause of infection after pediatric liver transplantation. Earlier detection of EBV could result in shortening the delay in diagnosis and allow better management of a pediatric high risk population. OBJECTIVES: To determine the timing of EBV primary infection after graft and to compare the performances of different assays for an early detection of the virus. METHODS: Sixty pediatric liver graft recipients were followed. Kinetics of appearance of different EBV serologic parameters (anti-EBV-IgG, -IgM and -IgA, and anti-EBV nuclear antigen-IgG) and of the viral DNA in peripheral blood lymphocytes by PCR were compared. RESULTS: Thirty-six patients had a primary EBV infection. The first PCR and IgM positive result appeared after a mean delay of 56 and 61 days, respectively, and preceded the IgG response (mean delay, 143 days). Most of the studied patients (13 of 16) developed anti-EBV-IgA and only 3 developed anti-EBNA-IgG during the follow-up period. CONCLUSIONS: EBV primary infection occurred in most cases during the first 2 months after graft. The IgG response was delayed. The best performance was obtained by PCR. However, the IgM test compared well with the PCR and could be a more widely accessible measure to follow regularly.

Adolescent↗

Increased risk of cytomegalovirus transmission in utero during late gestation.

OBJECTIVE: To determine whether the rate of human cytomegalovirus transmission in utero is related to the gestational age at the time of maternal infection. METHODS: One hundred twenty-three pregnant women followed in our units between 1988 and 1998 were studied retrospectively. Each had developed a primary infection with cytomegalovirus evidenced by a seroconversion, confirmed by specific enzyme immunoassays. Infants were diagnosed by urine culture. RESULTS: Regardless of gestational age at the time of maternal cytomegalovirus seroconversion, the mean rate of intrauterine transmission was 57.5%. There was a statistically significant difference between early seroconversion (during the first trimester) and late seroconversion (during the third trimester) (36.0% versus 77.6%; P < .001). The risk of transmission calculated for seroconversion during the second trimester was intermediate (44.9%). CONCLUSION: A statistically significant difference in the rate of intrauterine cytomegalovirus transmission was observed according to the duration of pregnancy at which primary infection occurred. The rate of transmission increased with gestational age.

Adult↗

Two new human T-lymphotropic virus type I phylogenetic subtypes in seroindeterminates, a Mbuti pygmy and a Gabonese, have closest relatives among African STLV-I strains.

Six new HTLV-I strains from seroindeterminate individuals were analyzed: four from Gabon, one from a Mbuti Efe pygmy in Congo (formerly Zaire), and one from a Congolese patient residing in Belgium. The LTR and env regions were sequenced and phylogenetic analyses were performed to characterize the new strains. Nucleotide divergence and phylogeny results showed that four of the new strains belong to the HTLV-Ib Central African subtype. The other two strains, one from the Efe pygmy and one from Gabon, lie on distinct branches of the LTR and env trees with respect to the four major HTLV-I subtypes. Despite the low bootstrap values, likelihood mapping analyses proved that these strains can be considered two new HTLV-I molecular subtypes, putatively named HTLV-Ie and HTLV-If. A relation exists in the phylogenetic trees and in the likelihood maps between the new subtypes and African STLV-I strains from Papio spp. and Cercopithecus spp., suggesting one or more interspecies transmission events in the past. This study demonstrates that the phylogenetic subtyping of HTLV-I in the African continent is far from being completed and that samples presenting an indeterminate serology can potentially belong to new subtypes in humans. In addition, present day serological tests do not reliably type strains within the HTLV-Ib Central African subtype.

Base Sequence↗

The simian T-lymphotropic virus STLV-PP1664 from Pan paniscus is distinctly related to HTLV-2 but differs in genomic organization.

We have isolated a highly divergent simian T-lymphotropic virus, STLV-PP1664, from a wild-caught bonobo (Pan paniscus). Previous phylogenetic analysis suggested that this virus represents an additional type of STLV but this has now become a matter of discussion. We have now obtained and analyzed the entire genome of STLV-PP1664. All major genes and their corresponding viral messengers were identified. Sequence comparison and phylogenetic analysis indicated that this virus, together with the closely related panp isolate, belongs to an early lineage within the PTLV-2 clade, differing from HTLV-2 by about 25%. In contrast to the HTLV-1 and HTLV-2 LTR, only two 21-bp repeats instead of three were found in the STLV-PP1664 LTR. Additional messengers, resulting from alternative splicing, potentially encode five different accessory proteins from open reading frames in the pX region: prorfI, porfII, ptorfV', and two isoforms of Rex. The amino acid sequences of these proteins are only distinctly related to the accessory proteins from HTLV-2. These data suggest a different genomic organization of the STLV-PP1664 pX region than that of HTLV-2. We conclude that STLV-PP1664, although related to HTLV-2, has some distinct features in the LTR and the pX regions, the impact of which needs further investigation. Although arguments pro and contra a distinct classification are nearly equally balanced, we propose to classify this virus as an STLV-2, designated STLV-2PP1664.

Amino Acid Sequence↗

Evolutionary rate and genetic heterogeneity of human T-cell lymphotropic virus type II (HTLV-II) using isolates from European injecting drug users.

Seven new Italian and two new British HTLV-II isolates were obtained from injecting drug users and the entire long terminal repeat (LTR) region was sequenced. Restriction analysis showed that all the Italian isolates are of the IIb subtype, whereas the British isolates are of the IIa subtype. To understand whether the further differentiation of each two principal HTLV-II subtypes in several subgroups could be statistically supported by phylogenetic analysis, the neighbor-joining, parsimony, and maximum likelihood methods were used. The separation between IIa and IIb is very well supported by all three methods. At least two phylogenetic subgroups exist within the HTLV-IIa and at least three within the HTLV-IIb subtype. In the present analysis, no statistical support was obtained for additional phylogroups. Two particular subgroups seem interesting because they include all European and North American injecting drug user strains within the IIa and IIb subtypes, respectively. These data confirm that European HTLV-II infection among drug users is probably derived from North America. They also suggest that though a certain differentiation by restriction analysis in different subgroups is possible, carefully interpreted phylogenetic analyses remain necessary. Using the likelihood ratio test, a molecular clock for the drug user strains was calibrated. A fixation rate between 1.08 x 10(-4) and 2.7 x 10(-5) nucleotide substitutions per site per year was calculated for the IIa and IIb injecting drug user strains. This is the lowest fixation rate so far reported for RNA viruses, including for HIV, which typically range between 10(-2) and 10(-4).

Biological Evolution↗

Avidity of IgG antibodies distinguishes primary from non-primary cytomegalovirus infection in pregnant women.

BACKGROUND: Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from non-primary infection in pregnant females. IgM tests often used for this purpose are not reliable enough. OBJECTIVE: To evaluate an HCMV-IgG urea-elution assay for its ability to distinguish primary from non-primary infection. In this assay, soaking the antigen-antibody complex with an urea containing solution frees antibodies with low avidity but has no influence on those with high avidity. An avidity index (AI) was calculated: AI = (OD with urea/OD without urea) x 100. STUDY DESIGN: HCMV-IgG avidity was measured on a single serum of 79 patients with past infection (pregnant women, graft recipients and blood donors) and of 63 patients (78 sera) with documented seroconversion (pregnant women and graft recipients). Sixty-one pregnant women positive or equivocal for HCMV-IgM but without a documented seroconversion were included in this study. RESULTS: Most (72/79) of the patients with past infection had an AI > 65% and all but one had an AI > 50%. In pregnant women, in the case of a primary infection within the past 3 months, AI are usually (51/53) < 50% and never > 65%. Among the IgM positive pregnant women who lack a seroconversion history, 38 had AI > 65% suggestive of an infection that had occurred at least 3 months earlier, 11 had an AI in a grey area between 50 and 65% and 12 had an AI < 50%, suggestive of a recent primary infection. CONCLUSIONS: In pregnant women, measurement of the IgG avidity may help to date a HCMV infection, an AI > 65% highly suggests a past infection while an AI < 50% corresponds to a recent primary infection.

Antibody Affinity↗

GB virus C: a novel pathogen or a curiosity for virologists?

The recently identified GB virus C is a flavivirus related to the hepatitis C virus. It appears quite prevalent in the general population and especially in individuals at risk of parenteral transmission. Many questions remain, most importantly the pathogenic role of the virus. It is unlikely that this virus has a major role in hepatic disease.

Flaviviridae↗

African origin of human T-lymphotropic virus type 2 (HTLV-2) supported by a potential new HTLV-2d subtype in Congolese Bambuti Efe Pygmies.

We identified a potential new subtype within human T-cell lymphotropic virus type 2 (HTLV-2), HTLV-2d, present in members of an isolated Efe Bambuti Pygmy tribe. Two of 23 Efe Pygmies were HTLV-2 seropositive, with HTLV-2 Western blot and enzyme-linked immunosorbent assay reactivities. From one of them the entire genome of the HTLV-2 strain Efe2 could be amplified and sequenced. In all gene regions analyzed, this strain was the most divergent HTLV-2 strain, differing by 2.4% (tax/rex) to 10.7% (long terminal repeat) from both subtypes HTLV-2a and HTLV-2b, yet major functional elements are conserved. The similarity between the HTLV-2 Efe2 Gag and Env proteins and the corresponding HTLV-2a and -2b proteins is consistent with the observed serological reactivity. In the proximal pX region, one of the two alternative splice acceptor sites is abolished in HTLV-2 Efe2. Another interesting feature of this potential new subtype is that it has a Tax protein of 344 amino acids (aa), which is intermediate in length between the HTLV-2a Tax protein (331 aa) and the HTLV-2b and -2c Tax proteins (356 aa) and similar to the simian T-cell lymphotropic virus type 2 (STLV-2) PP1664 Tax protein. Together these two findings suggest a different phenotype for the HTLV-2 Efe2 strain. Phylogenetic analyses confirmed that the Pygmy Efe2 strain potentially belonged to a new and quite divergent subtype, HTLV-2d. When the STLV-2 bonobo viruses PP1664 and PanP were used as an outgroup, it was clear that the Pygmy HTLV-2 Efe2 strain had the longest independent evolution and that HTLV-2 evolution is consistent with an African origin.

Amino Acid Sequence↗

Molecular analysis of GB virus C isolates in Belgian hemodialysis patients.

GB virus C (GBV-C) has been detected in Belgian hemodialysis patients. To study their genomic diversity and phylogenetic relationship, a 592 nucleotide fragment extending from the 5' non-coding region to part of the E1 gene of the GBV-C genome was amplified and sequenced from 12 Belgian hemodialysis patients in two different centers. Together with strains from different geographical origins, these sequences were analyzed phylogenetically using three different methods. A consistent tree topology was obtained with all methods. Three GBV-C genotypes were observed with two subtypes in type 2 and a questionable subtyping in type 1. Except for one isolate falling into type 1 cluster which mainly consists of African strains, all the other Belgian strains clustered within the type 2a branch. Two GBV-C isolates in two patients from the same hemodialysis center clustered together closely, suggesting a nosocomial transmission. In view of their long branch length, it seems unlikely that the other Belgian strains evolved recently from a common ancestor. Our results indicate that the major type circulating among Belgian hemodialysis patients seems to be 2a, which is usual for Europe and North America, but that the African type 1 also exists to a minor extent. Although patient to patient transmission of GBV-C in Belgian hemodialysis centers did occur, it may not account for the majority of infections.

Base Sequence↗