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Biomedical subjects

U Dietrich

Publications and source records attributed to U Dietrich.

At least 55 records · Page 3Linked to original sources

Molecular epidemiology of HIV in Israel.

The aim of this study was to identify the HIV types and subtypes prevalent in Israel among different populations in terms of risk or geographic origin of the HIV infection. A total of 149 blood samples were collected from HIV-positive persons from different risk groups for HIV infection who were living in Israel. HIV subtyping was performed by a V3-based peptide enzyme immunoassay, supplemented by direct sequencing of polymerase chain reaction products from the V3 region. Multiple HIV-1 subtypes were shown to circulate in Israel; whereas most of the infections among Israelis and Palestinians were of subtype B, infections among the large Ethiopian population in Israel were caused by HIV-1 subtype C. Occasionally, we found HIV-1 subtypes A and D and a putative B/C recombinant. No HIV-2 infection was identified. Sequence comparisons and phylogenetic tree analyses point at multiple introductions of HIV into the country. The presence of mainly two different HIV-1 subtypes, B and C, in two separated populations in Israel may result in two distinct epidemiologic patterns among HIV-infected individuals in Israel. Subtype C infection among the Ethiopians in Israel opens new research avenues toward better understanding the natural history of infection with HIV-1 subtype C in Ethiopians living in a Western society compared with those living in Ethiopia.

Amino Acid Sequence↗

[Serotypes of the human immunodeficiency virus type 1 in Madrid].

BACKGROUND: HIV-1 shows high genetic variability, mainly in the genomic region codifying the envelope proteins, which are the most immunogenic. This fact explains the high heterogeneity of antibodies against HIV-1 epitopes. Both genetic and serologic diversity has allowed to classify HIV-1 variants in several subtypes (genotypes and serotypes, respectively). The clinical and epidemiological significance of infection caused by each subtype remains to be clarified. PATIENTS AND METHODS: Serum samples from 154 HIV-seropositive individuals living in Madrid were studied. Serotyping was performed using 4 peptides belonging to the V3 env region. Epidemiological and clinical variables examined in these patients were the route of infection, the year in which HIV infection occurred, the country of birth, and the rate of disease progression (rapid versus slow). RESULTS: 148 (96.2%) samples could be serotyped, and the B class was recognized in 131 (88.5%) of them. Serotype A/C was found in 9 (6.1%). Two samples (1.3%) reacted to peptide E; however, both were also reactive against the B peptide, suggesting co-infection with B and E subtypes. Six samples were EIA-reactive for HIV-1/2 but were typed as HIV-2 alone. Infection with serotypes A/C was more frequent amongst immigrants, mainly in Africans. There was not association between any subtype and the route of infection neither a different rate of disease progression. CONCLUSION: HIV-1 serotype B is the most frequently found in HIV-seropositive individuals living in Madrid, without association with the route of infection or the clinical course of the disease. Serotypes A/C and E were found sporadically, mainly among immigrants.

Africa↗

[Critical evaluation of vascular embolization in patients with Rendu-Osler disease].

BACKGROUND: As causal therapy of Rendu-Osler-Weber syndrome is not yet possible, there are many different therapeutical approaches. It seemed expedient to investigate the efficacy of super-selective angiography in treating Rendu-Osler-Weber syndrome after this technique proved effective in other therapeutic settings. This method is known to be efficient in controlling tumor bleeding. PATIENTS: Between March 1993 and September 1995, eight patients with an average age of 57 years were treated by super-selective intraarterial embolization. RESULTS: In all cases epistaxis occurred on both sides. Unilateral embolization was performed in ten cases and bilateral embolization in five cases. In two of three patients with nasal packing the embolization permitted removal of the packing. Nevertheless nosebleeds reoccurred on an average of 3.5 days after therapy. Two of eight patients showed long-term improvement after therapy. They suffered fewer nosebleeds than before. Complications included one patient who suffered from partial hemiparesis after embolization, which lasted 1.5 hours and was completely reversible. Another patient died because of pulmonic bleeding caused by manifestation of the disease in this organ. Often patients complained of facial pain or headache which occasionally lasted for a few weeks. CONCLUSIONS: Endovasal embolization obviously is an alternative to artery ligation in emergency cases whereas the long-term success is currently impaired by formation of new anastomoses. Further development of this technique is necessary.

Adult↗

Structure and genomic organization of a novel human endogenous retrovirus family: HERV-K (HML-6).

Prototypic elements of a novel human endogenous retrovirus (HERV) family were identified and cloned from a human genomic library by the use of a pol fragment, HML-6, related to type A and type B retroviruses and class II HERVs. Out of 39 polhybridizing clones, five contained structures of full-length retroviral proviruses, with regions showing similarity to gag, pol and env, flanked by long terminal repeats (LTRs). Restriction mapping and partial sequence analysis of each full-length clone revealed few conserved restriction sites among HML-6 genomes, and about 20% sequence divergence over the reverse transcriptase region sequenced, suggesting that HML-6 constitutes a heterogeneous, but distinct family of elements belonging to the HERV-K superfamily. Sequence analysis of two clones, HML-6p and HML-6.17, revealed a lysine (K) tRNA UUU primer-binding site, and 40-68% nucleotide sequence similarity to LTR, gag, pro, pol and env regions of type B retroviruses and class II HERVs. HERV-K (HML-6) elements are present at about 30-40 copies per haploid genome. The HML-6 LTRs contain putative progesterone-responsive elements, which may be involved in the regulation of HML-6 expression. Furthermore, there are about 50 additional solitary HML-6 LTRs per haploid genome. Such LTRs were integrated within the pol region of two clones belonging to the same HML-6 family, indicating that some site preference may be involved in HERV integration.

Amino Acid Sequence↗

Diversity of antibody binding to V3 peptides representing consensus sequences of HIV type 1 genotypes A to E: an approach for HIV type 1 serological subtyping.

We investigated whether V3-binding assays might be useful to analyze human immunodeficiency virus type 1 (HIV-1) variants in different geographic regions. We showed that strong cross-reactivity between subtype-specific V3 peptides is almost inevitable in standard indirect enzyme-linked immunosorbent assays (EIA), impairing precise serological subtyping. We therefore developed a subtype-specific EIA (HIV-1 SSEIA) that uses the principle of blocking by an excess of peptide in the liquid phase. Using 231 serum samples collected from HIV-1-infected individuals in 10 different geographical areas from 4 continents, we showed that this approach detected the dominant subtype reactivity in more than 97% of the cases. Internal controls (0 and 100% blocking) were used for every sample such that comparative analysis was possible, independent of both the individual humoral response and the time of collection during the course of infection. This was validated by the excellent concordance of the serological profiles of couples and the temporal stability of the serological profile in individuals. The geographical distribution of the various subtypes in the SSEIA was in agreement with the present knowledge of the distribution of the various genotypes. Although the goal of this study was not an extensive seroepidemiological survey, our results showed that the various profiles in most of the regions were relatively homogeneous, but in central Africa there was a large diversity of serological profiles. Cluster analysis identified a limited number of V3 serogroups of serotypes within the HIV-1 group M. Five serogroups, some of them divided into subgroups, were identified and characterized by a mean serological profile. Our data confirmed that subtypes A and C, although being dissimilar genetic subtypes, present conserved antigenic properties in the V3 region, and that the D subtype is probably the most divergent within the group M (B Korber et al., J Virol 1994;68:6730). Cluster analysis showed a clear correlation between position within the dendrogram and geographical origin of the samples. This is further support for the reliability and thereof the usefulness of the SSEIA. This simple methodology may help facilitate the analysis of the distribution of various HIV-1 subtypes circulating in different populations and regions.

Amino Acid Sequence↗

Secondary structural elements as a basis for antibody recognition in the immunodominant region of human immunodeficiency viruses 1 and 2.

Synthetic peptide antigens corresponding to the entire third variable region V3, the principal neutralizing determinant of the human immunodeficiency virus (HIV) envelope glycoprotein of HIV-1 subtype B (1), HIV-2 subtype A (5), and HIV-2 subtype B (7) were synthesized by solid-phase peptide synthesis (Table 1). 1 and 5 were also prepared as their GlcNAc-glycosylated forms at the natural N-glycosylation site NXT (positions 6-8; peptides 4 and 6). Additionally, the proposed beta-turn region of 1 (GPGR; positions 15-18) was altered by introducing D-Ala17 (2) and D-Pro16 (3). All compounds have been studied by two-dimensional NMR techniques. Interproton distances and 3JNH/H alpha coupling constants derived from NMR data are used as restraints in distance geometry and ENSEMBLE-Distance and angle-bound driven dynamics calculations. The stimulations led to disordered conformations except for a high propensity of a beta II-turn in the region GPXR (positions 15-18) in 1, 2, and 4. In 3 (G-D-ProGR, positions 15-18), a type beta I'-turn was mainly found instead. For peptide 7, the consensus sequence of HIV-2 subtype B, a type beta II-turn was also found although the primary structure (VSGL; positions 15-18) differs grossly from the HIV-1 peptide 1. With the exception of 2, all beta II-turns were able to form a canonically opened beta-turn by a 180 degree rotation of phi(G17). Surprisingly, compounds 5 and 6 that are highly similar to 7 showed no beta II-type turn within MSGL (positions 15-18). They form a type beta VIII-turn across the tetrapeptide SGLV (positions 16-19) together with a non-canonical turn conformation across LMSG (positions 14-17) leading to an S-conformation. The reaction of the peptides with HIV-positive sera from patients infected with different subtypes of HIV-1 and HIV-2 was tested in enzyme-linked immunosorbent assays (ELISA reactions). No HIV-2 sera reacted peptide 1 and no HIV-1 sera showed reactivity to peptide 5. We propose that certain amino acid exchanges within the V3 domain lead to altered conformations of the V3 loop resulting in antibodies that show altered binding properties to the peptide antigens used in the ELISA reactions.

Amino Acid Sequence↗

The epidemiology of HIV in India.

India is the first country outside Africa where an HIV-2 epidemic is running in parallel to an HIV-1 epidemic, resulting in a significant proportion of double infections. HIV is spreading rapidly, mainly by heterosexual contact, but also among intravenous drug users. Genetic analyses of the HIV variants circulating in India point towards HIV-1 and HIV-2 having been introduced into the country recently.

Adult↗

Continuity and discontinuity in the anti-V3 IgG response of human immunodeficiency virus type 1-infected persons in a cross-sectional and longitudinal study using synthetic peptides.

The principal neutralization domain (PND) of the V3 region of human immunodeficiency virus type 1 (HIV-1) gp120 is central to HIV pathogenesis. The IgG antibody response to PND was followed in 15 HIV-1-infected persons from southern Sweden over 2-5 years using 32 synthetic V3 peptides. Five peptides had amino acid sequences derived from isolates from each of 5 patients. Sera obtained simultaneously with isolate almost always reacted strongly with these cognate peptides; however, reactivity was undetectable in 1 patient's serum and short lived in the sera of another, indicating inducible holes in the antibody repertoire, which would facilitate dissemination of the corresponding virus strains. Reactivity to other V3 peptides correlated with sequence similarity to the cognate peptide. Strong, stable reactivity to peptides with sequences similar to a south Swedish V3-consensus was accompanied by transient activity to less similar ones. The latter may reflect viral variation, B lymphocyte clonal depletion, or both. Certain IgG responses appeared to preclude others, suggesting clonal dominance.

Acquired Immunodeficiency Syndrome↗

High proportion of HIV-2 and HIV-1/2 double-reactive sera in two Indian states, Maharashtra and Goa: first appearance of an HIV-2 epidemic along with an HIV-1 epidemic outside of Africa.

The seroprevalence of HIV-1 and HIV-2 infections was determined in selected groups of patients from an STD clinic and in female prostitutes from two different states of India. A total of 809 sera from Maharashtra and of 61 sera from Goa were analyzed. Of the unscreened sera from Bombay, 39% were positive as were 15% of the sera from Goa. Among the HIV-positive sera from Bombay, 79% were positive for HIV-1, 4% were positive for HIV-2 and 17% were positive for HIV-1 and 2. In the Goa group, 67% of the infected sera were HIV-1-positive and 33% were HIV-2 positive. Due to the nearly even distribution of infections between men and women, a mainly heterosexual mode of transmission is evident. HIV-2 infections were first detected in India in 1990 (Rübsamen et al., Lancet, 1991). Before that time, Asia was believed to be free HIV-2. The present study represents the first documentation of a large proportion of these infections, alone and in combination with HIV-1, in the Asian continent. An HIV-2 epidemic running parallel to an HIV-1 epidemic so far has never been observed outside of Africa. This would indicate that a further spread of HIV-2 worldwide is to be expected and that HIV-2 should be included in programs of vaccine development for humans.

Blotting, Western↗

Genetic analysis of human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) mixed infections in India reveals a recent spread of HIV-1 and HIV-2 from a single ancestor for each of these viruses.

DNA sequences encoding the surface envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) were amplified by PCR from uncultured peripheral blood mononuclear cells obtained from patients with serologically defined HIV-1/HIV-2 mixed infections from Bombay, India. HIV-1-specific PCR products were obtained in seven of seven randomly chosen doubly reactive cases, while HIV-2-specific sequences were detected in five of seven cases (71%). DNA sequence analysis showed that the HIV-1 gp120 coding sequences were closely related to each other (nucleotide sequence divergence of between 3.1 and 6.8%). Phylogenetic tree analysis placed the Indian strains within the C subtype of HIV-1, being most similar to sequences previously found in East and South Africa. The HIV-2 sequences were also closely related to each other, with an overall sequence divergence of between 5.6 and 10.5%. The low level of nucleotide divergence among Indian HIV-1 and HIV-2 sequences suggests a fairly recent introduction of each virus into this population from a single point of entry in each case. The HIV-2 sequences reported here represent the first analysis of Asian HIV-2 strains and confirm the serological pattern previously detected in India. These data show that a substantial spread of HIV-2, together with HIV-1, has appeared outside Africa in a population hitherto unexposed to HIV. These findings imply that further spread of HIV-2 worldwide is to be expected and have important implications for future vaccine and therapy development.

Acquired Immunodeficiency Syndrome↗