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J Albert

Publications and source records attributed to J Albert.

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

Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effects of inhaled nitric oxide compared with aspirin on platelet function in vivo in healthy subjects.

1. Nitric oxide has platelet-stabilizing effects. Inhaled nitric oxide is used to treat pulmonary disorders, and may prolong bleeding times, suggesting that it has effects on haemostasis. We therefore examined if inhaled nitric oxide influences platelet function in vivo in healthy subjects. 2. Platelet aggregability (filtragometry ex vivo, which reflects aggregability in vivo), bleeding time and platelet secretion products and cGMP in plasma were studied during inhalation of two different doses of nitric oxide (30 and 80 p.p.m.; 15 min at each dose level; n = 19) and during prolonged (55 min; n = 18) inhalation of 30 p.p.m. nitric oxide. For comparison, studies were also performed before and after ingestion of 640 mg aspirin in 13 of the healthy subjects. 3. Plasma cGMP increased dose dependently during nitric oxide inhalation, suggesting guanylate cyclase activation in vivo. Platelet aggregability was, however, little affected and platelet secretion was not attenuated by nitric oxide inhalation. Bleeding time tended to increase (by 16-33%), but was significantly increased only after prolonged inhalation of nitric oxide at 30 p.p.m. 4. Aspirin (640 mg orally) caused pronounced and significant prolongations of filtragometry readings and bleeding time. Thus, the methods used were able to reveal platelet stabilization. 5. We conclude that nitric oxide inhalation causes only mild, if any, attenuation of platelet function in healthy subjects with a normal endogenous nitric oxide production. The effects may be different in disease states.

Administration, Inhalation↗
PubMed1996

Quantification of HIV-1 using multiple competitors in a single-tube assay.

Methods for quantification of human immunodeficiency virus type 1 (HIV-1) based on competitive PCR and fragment analysis have been developed. Samples containing HIV-1 DNA and known amounts of three cloned competitors were co-amplified by PCR with semi-nested primers. The competitor DNAs contained the same long terminal repeat primer binding sequences as the wild-type DNA, but they are different in internal sequences and length. One of the inner primers was fluorescent-labeled to allow discrimination between the wild-type DNA and the three competitors by fragment analysis using a standard automated sequencer. A calibration curve using the peak area of the three competitors enabled accurate determination of target amount with minimal variations. The method presented here can be used for quantification of HIV-1 in clinical samples and will be useful for monitoring disease progression and treatment effects.

Base Sequence↗
PubMed1995

Biological and molecular characterization of subtype D, G, and A/D recombinant HIV-1 transmissions in Sweden.

HIV-1 can be subdivided into at least nine genetic subtypes (A through H and O), but in Europe and the United States there is an almost complete dominance of subtype B. In this study three Swedish HIV-1 transmission chains of subtypes other than subtype B have been biologically and molecularly characterized. The three index cases were African men. The p17 gag and env V3 regions of the HIV-1 genome were directly sequenced from uncultured lymphocytes. Phylogenetic analyses showed that the HIV-1 variants with each transmission group were genetically closely related, supporting the epidemiological information. The individuals in transmission groups I (n = 3) and II (n = 2) carried subtype G and D virus, respectively. Interestingly, all four individuals in transmission group III displayed a recombinant genotype with subtype D p17 gag sequence and subtype A V3 sequence. The biological phenotype of virus isolates (rapid/high, syncytium-inducing; or slow/low, non-syncytium-inducing) correlated with the clinical stage of the infected individual. The study also suggested that the correlation between biological phenotype and V3 genotype that has been established for subtype B HIV-1 variants may be valid also for other subtypes. This study demonstrates that HIV-1 variants of subtypes other than B, including a subtype A/D recombinant, are being transmitted in Europe.

Adult↗
PubMed1995

Long-term protection against SIV-induced disease in macaques vaccinated with a live attenuated HIV-2 vaccine.

The aim of this study was to test the ability of a live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine to protect cynomolgus monkeys against superinfection with a pathogenic simian immunodeficiency virus (SIVsm). This report is an update on our previously reported observation period of nine months. The new data here show that three of four monkeys vaccinated with live HIV-2 were protected against immunosuppression and SIV-induced disease during more than five years of follow-up. The quality of the immunity was permissive for infection, but monkeys that survived showed restricted viral replication in peripheral blood and lymph nodes. This study shows that it is possible to induce protection against a pathogenic heterologous primate lentivirus and to prevent disease in vaccinated monkeys even if infection is not prevented. These findings provide evidence that protection against AIDS can be achieved by immunization.

AIDS Vaccines↗
PubMed1994

Stable biological and antigenic characteristics of HIV-2SBL6669 in nonpathogenic infection of macaques.

The purpose of the present study was to investigate if the biological and antigenic properties of human immunodeficiency virus type 2 change over time in cynomolgus macaques (Macaca fascicularis) experimentally infected with HIV-2SBL6669. Sequential virus isolates and serum samples were obtained during a 2-year period and studied in autologous neutralization assays. All six macaques studied seroconverted shortly after infection and remained healthy during the observation period. Virus could be isolated from all six animals during the first 100 days postinfection. Thereafter four monkeys became virus isolation negative, either permanently or transiently (two macaques each), whereas two macaques remained virus isolation positive during the entire observation period. Sequential reisolates from the macaques invariably replicated in HUT-78, U937-2, and Jurkat-tat cell lines, similarly to the HIV-2SBL6669 inoculum virus. The ability to produce neutralizing antibodies correlated with positive virus isolations, hence four macaques produced neutralizing antibodies against inoculum virus and sequential reisolates. Once the neutralizing antibody appeared, sequential reisolates obtained at both early and late time after infection were neutralized, indicating that the neutralizing epitopes of the virus are conserved in the infected animals over time. This is different from the pathogenic SIVsm infection in macaques or HIV-1 infection in humans, where emergence of neutralization resistant variants seems to be the rule. In contrast, in HIV-2-infected macaques the biological properties of the virus are stable and the neutralizing antibody response shows extensive cross-reactivity.

Animals↗
PubMed1994

Direct covalent attachment of small peptide antigens to enzyme-linked immunosorbent assay plates using radiation and carbodiimide activation.

Direct adsorption of small peptide antigens to unaltered, commercially available polystyrene surfaces may be too weak to permit suitable assay by ELISA. We therefore developed a simple method for the covalent attachment of small, potentially single epitope antigens to polystyrene surfaces. Chemical activation of polystyrene plates with carbodiimide considerably improves the total and covalent attachment of radioactive octapeptides. The covalent attachment was demonstrated by washing with hot detergent. A 3.5 Mrad gamma-irradiation of plates also increases total binding, particularly in combination with chemical activation. The covalent attachment presumably occurs through formation and chemical activation of carboxylate functions on the polystyrene surface which form amide bonds with peptides. ELISA test was performed with CGRP and successive smaller CGRP fragments. Covalent attachment of C-terminal peptide fragments as detection antigens allows optimal recognition and sensitivity even for hexapeptides, while decapeptide antigens were already poorly recognized using a conventional antigen plating technique. Repetitive detergent washes and/or prolonged storage of plates with covalently bound antigens did not reduce their ELISA sensitivity. The method with storage and reutilization capacities that we present here will be useful for the development of preplated antibody screening test.

Antigens↗
PubMed1994

The biological phenotype of HIV-1 is usually retained during and after sexual transmission.

The biological phenotype of HIV-1 isolates from 21 subjects with primary HIV-1 infection was determined in primary lymphocytes and monocyte-derived macrophages as well as in three T-cell lines (MT-2, HUT78, and C8166). Seven isolates (33%) replicated on at least one cell line and were classified as rapid/high (n = 6) or intermediate (n = 1), while 14 isolates (67%) did not replicate in cell lines and were classified as slow/low. All isolates replicated in primary monocyte-derived macrophage cultures. Studies on 10 pairs consisting of index case and seroconverting sexual partner showed that the biological phenotype of HIV-1 was unchanged in nine transmissions, including 5 pairs where a rapid/high virus was transmitted. Most individuals (5 of 6) infected by a rapid/high virus retained this phenotype after seroconversion. These individuals also had significantly lower CD4 lymphocyte counts 1-3 years after infection. Thus, in contrast to what has been suggested by others, we found that HIV-1 variants with rapid/high phenotype were usually not suppressed, neither during sexual transmission nor after seroconversion in the new host. These findings have important implications for the understanding of HIV-1 transmission and pathogenesis as well as for vaccine design.

Cell Line↗
PubMed1994

Comparison of the sensitivities of primary isolates of HIV type 2 and HIV type 1 to antiviral drugs and drug combinations.

The sensitivity of primary isolates of HIV-2 to the antiretroviral drugs 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI), and 3'-fluoro-3'-deoxythymidine (FLT) was measured in vitro in PBMCs and compared to that of primary isolates of HIV-1. HIV-2 isolates showed a similar sensitivity to the drugs compared to HIV-1 isolates. Both the relative and the absolute potencies of the three drugs were similar for inhibition of HIV-1 or HIV-2 replication. The effect of combinations of the antiviral drugs was also studied. The combinations of AZT plus FLT, AZT plus ddI, and FLT plus ddI showed synergistic inhibition of three primary HIV-2 isolates, similar to that previously shown for primary HIV-1 isolates. These results indicate that primary isolates of HIV-2 from untreated persons show a level of sensitivity to antiviral nucleoside analogs similar to that shown by HIV-1 isolates, and are also synergistically inhibited by drug combinations shown to be synergistic against HIV-1. Therapeutic regimes with nucleoside analogs used clinically against HIV-1 infection may therefore also be similarly useful against infection with HIV-2.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Impaired parathyroid hormone release in human immunodeficiency virus infection.

Patients with human immunodeficiency virus type 1 (HIV-1) seropositivity exhibited significantly lower intact serum parathyroid hormone (PTH) values (mean, 13.6 ng/liter; n = 44) than healthy controls (mean, 38.1 ng/liter; p < 0.001; n = 50). The reduction was greater among patients with no or mild immunodeficiency (> 400 x 10(6) CD4+ lymphocytes/ml blood; n = 22) than in those with severe immunodeficiency (< 200 x 10(6) CD4+ lymphocytes/ml blood; n 22; p = 0.03), although total serum calcium was normal in all groups. Patients with severe immunodeficiency demonstrated an inverse correlation between total serum calcium and serum PTH (r2 = 0.367; p < 0.01), which was also present in healthy controls (r2 = 0.482; p < 0.001), but not among the seropositive patients with no or mild immunodeficiency (r2 = 0.017; p = 0.58). Parathyroid cells express a protein recognized by antibodies directed against CD4, the HIV-1 receptor. This implies that these cells may be directly infected with HIV-1 and also interact with circulating autoantibodies against CD4, thus resulting in impaired PTH release.

Autoantibodies↗
PubMed1994

Apparent selection against transmission of zidovudine-resistant human immunodeficiency virus type 1 variants.

The sexual transmission of zidovudine-resistant human immunodeficiency virus type 1 (HIV-1) variants was investigated in 5 donor-recipient pairs in which all donors and none of the recipients had received zidovudine treatment. The virus isolates were tested for sensitivity to zidovudine (IC50) in vitro using blood donor lymphocytes. A region of the HIV-1 pol gene was also directly sequenced by a solid-phase sequencing method. Four donors were shown to have zidovudine-resistant HIV-1 variants. Two of these patients had a single mutation (Thr215-->Tyr), and 2 had a double mutation (Met41-->Leu and Thr215-->Tyr) that previously has been shown to confer zidovudine resistance. Zidovudine-resistant virus was found in only 1 of the 4 recipients, which indicates that zidovudine-resistant HIV-1 variants may be selected against during transmission. Thus, the transmission of zidovudine-resistant HIV-1 variants is a complex process that will require consideration whenever zidovudine treatment is initiated in persons who may have been infected by resistant variants.

Adult↗
PubMed1994

MT-2 cell tropism of human immunodeficiency virus type 1 isolates as a marker for response to treatment and development of drug resistance.

The correlation of the tropism of human immunodeficiency virus type 1 (HIV-1) isolates for MT-2 cells with response to zidovudine and didanosine treatment and with development of drug resistance was studied. Patients with MT-2-negative but not MT-2-positive HIV-1 had a significant increase in CD4+ lymphocyte counts during the first 6 months of treatment. In both groups and for both drugs, the rate of CD4+ lymphocyte decline decreased after the start of treatment. MT-2-positive isolates were more likely than MT-2-negative isolates to show reduced sensitivity to zidovudine and didanosine. Because the differences in zidovudine sensitivity were first evident after 12 months of treatment, drug resistance was probably not the cause of poor response early in zidovudine treatment in patients with MT-2-positive HIV-1. Thus, patients with MT-2-positive virus have limited benefit from treatment with single nucleoside analogues. Knowledge of MT-2 cell tropism may be important in clinical trials and for choosing treatments for patients.

Adult↗
PubMed1994

Peptide serology for analysis of the inter- and intra-individual variation in the HIV-1 V3 domain.

OBJECTIVE: To investigate whether the specificity of antibody responses to the gp120 V3 domain in HIV-1-infected individuals is related to the variability of this region. METHODS: Sera from a cohort of 22 HIV-1-infected Ugandans were tested against peptides derived from each individual's autologous proviral V3 apex sequence. Autologous peptide reactivity was compared with reactivity to peptides derived from two Ugandan consensus sequences and previously isolated US/European and African viruses. Peptides from individuals with heterogeneous V3 apex sequences, representing different HIV-1 variants, were obtained and tested against the corresponding sera. RESULTS: A notable cross-reactivity to different V3 apex peptides was observed. However, in the majority of sera, antibody reactivity to the autologous peptides was found to exceed reactivity to any of the other peptides tested. V3 proviral sequences from the Ugandan cohort studied have been shown to be closely related to the HIV-1MN isolate and thus, their sera gave better reactivity to V3MN and related peptides than to peptides representing other African HIV-1 isolates. In individuals with heterogeneous V3 proviral sequences, we could distinguish divergent antibody responses to the genomic variants differing by single amino acids. CONCLUSION: Analysis of seroreactivity to peptides might constitute a relevant tool for investigating the variability of the HIV-1 gp120 V3 domain within infected populations and single individuals.

Amino Acid Sequence↗
PubMed1994

MT-2 cell tropism as prognostic marker for disease progression in human immunodeficiency virus type 1 infection.

The ability of human immunodeficiency virus type 1 (HIV-1) isolates to replicate in MT-2 cells was investigated as a prognostic marker for disease progression and CD4+ lymphocyte depletion in 53 HIV-1-infected, asymptomatic individuals. MT-2-negative viruses were isolated from 49% of the patients both early and late during the follow-up period; 38% converted from being MT-2 negative to MT-2 positive, while 11% were MT-2 positive throughout the study. One individual showed a fluctuating virus phenotype. The loss of CD4+ lymphocytes was significantly more rapid in MT-2-positive patients. We found a broad spectrum of CD4+ lymphocyte changes in patients whose virus changed its MT-2 tropism. Our data suggest that the changes could be divided into three general patterns. A stable or slowly decreasing CD4+ lymphocyte count changed into a more rapid fall in 44% of the patients, no significant change in rate of decline could be noted in 44% of the patients, while a stable CD4+ lymphocyte level after a change in MT-2 tropism was noted in 12% of the patients. A correlation between MT-2 tropism and clinical symptoms was also noted. Half of the patients with MT-2-negative virus throughout the study were still asymptomatic after a mean follow-up time of 80 months, while only 15% of those who converted remained asymptomatic. All patients with MT-2-positive viruses at the time of inclusion in the study developed HIV-1-related symptoms, and half of them died during the study. The MT-2 status of 16 patients, could be determined at the time of AIDS diagnosis; 50% were Mt-2 positive, while 50% were MT-2 negative. No difference in AIDS-defining diagnoses or CD4+ lymphocyte counts at the time of diagnosis was noted. Knowledge of the HIV-1 phenotype may improve the early recognition of progressive disease.

Adult↗
PubMed1994

Dual tropism for macrophages and lymphocytes is a common feature of primary human immunodeficiency virus type 1 and 2 isolates.

We have investigated the ability of human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates to infect and replicate in primary human macrophages. Monocytes from blood donors were allowed to differentiate into macrophages by culture in the presence of autologous lymphocytes and human serum for 5 days before infection. A panel of 70 HIV-1 and 12 HIV-2 isolates were recovered from seropositive individuals with different severities of HIV infection. A majority of isolates (55 HIV-1 and all HIV-2) were obtained from peripheral blood mononuclear cells, but isolates from cerebrospinal fluid, monocytes, brain tissue, plasma, and purified CD4+ lymphocytes were also included. All isolates were able to infect monocyte-derived macrophages, even though the replicative capacity of the isolates varied. Interestingly, isolates with a rapid/high, syncytium-inducing phenotype did not differ from slow/low, non-syncytium-inducing isolates in their ability to replicate in monocyte-derived macrophages. Others have reported that rapid/high, syncytium-inducing isolates have a reduced ability to infect and replicate in monocytes. However, different methods to isolate and culture the monocytes/macrophages were used in these studies and our study. Thus, the ability of HIV isolates to replicate in monocytes/macrophages appears to be strongly influenced by the isolation and culture procedures. It remains to be determined which culture procedure is more relevant for the in vivo situation.

Cell Line↗