Biomedical subjects

Kenth Gustafsson

Publications and source records attributed to Kenth Gustafsson.

4 recordsLinked to original sources

PubMed2005

HIV-1 incorporates ABO histo-blood group antigens that sensitize virions to complement-mediated inactivation.

ABO histo-blood group antigens have been postulated to modify pathogen spread through the action of natural antibodies and complement. The antigens are generated by a polymorphic glycosyl-transferase encoded by 2 dominant active and a recessive inactive allele. In this study we investigated whether ABO sugars are incorporated into the envelope of HIV-1 virions. HIV vectors derived from cells expressing ABO antigens displayed sensitivity to fresh human serum analogous to ABO incompatibility, and ABO histo-blood group sugars were detected on the viral envelope protein, glycoprotein 120 (gp120). Moreover, lymphocyte-derived virus also displayed serum sensitivity, reflecting the ABO phenotype of the host when cultured in autologous serum due to adsorption of antigens to cell surfaces. Serum sensitivity required both active complement and specific anti-ABO antibodies. Thus, incorporation of ABO antigens by HIV-1 may affect transmission of virus between individuals of discordant blood groups by interaction with host natural antibody and complement.

ABO Blood-Group System↗

PubMed2004

Evolution of the human ABO polymorphism by two complementary selective pressures.

The best-known example of terminal-glycan variation is the ABO histo-blood group polymorphism in humans. We model two selective forces acting on histo-blood group antigens that may account for this polymorphism. The first is generated by the invasion of opportunistic bacterial or other pathogens that interact with the epithelial-mucosal surfaces. The bacteria adapt to the microenvironments of common host phenotypes and so create frequency-dependent selection for rarer host alleles. The second is generated by intracellular viruses, and accounts for the observed differentials between the ABO-phenotype frequencies. It is thought that viruses acquire histo-blood group structures as part of their envelope from their previous host. The presence of host antigens on the viral envelope causes differential transmission of the virus between host types owing to the asymmetric action of ABO natural antibodies. Our model simulations show that these two forces acting together can account for the major features of the ABO polymorphism in humans.

ABO Blood-Group System↗

PubMed2003

Modulation of adenovirus infection in vitro by antisense oligodeoxynucleotides.

OBJECTIVE: Antisense oligodeoxynucleotides (ODNs) may represent a novel, airway directed approach to the treatment of adenovirus infection of the lung, for which no specific therapy exists. This study assessed the efficacy of antisense ODNs in modulating adenovirus infection in vitro. METHODOLOGY: A biological assay, which quantified viral plaque formation by wild type adenovirus 5 in a lung epithelial cell line (A549), was used to evaluate the inhibitory effect of a number of antisense ODNs targeted to the early (E) 1 A and protein IX genes of adenovirus 5. Antisense ODNs (20-21mers, phosphorothioate end-protected) were designed to straddle the initiation of translation (AUG) codon of the mRNA of the targeted gene. RESULTS: There was a consistent and significant (P < 0.005) reduction in viral plaque formation in those cells treated with an E1A antisense ODN, compared with the nonsense control ODN. Neither the addition of a cationic lipid (Lipofectamine), nor increasing the concentration of ODN from 1 micro mol to 15 micro mol enhanced the original inhibitory effect observed with the E1A antisense ODN. CONCLUSIONS: An antisense ODN targeted to the E1A gene can specifically inhibit adenovirus 5 infection in vitro, suggesting a potential therapeutic role for antisense ODNs in adenovirus infection of the lung.

Adenoviridae↗

PubMed2002

Expression of ABO or related antigenic carbohydrates on viral envelopes leads to neutralization in the presence of serum containing specific natural antibodies and complement.

No definitive biologic function has been associated with the human ABO histo-blood group polymorphism, or any other terminal carbohydrate differences within or between closely related species. We have experimentally addressed the question of whether viral particles can become glycosylated as determined by the glycosylation (eg, ABO) status of the producer cell and as a result be affected by human serum containing specific natural antibodies (NAbs). Measles virus was produced in cells transfected with cDNA encoding, either human A-transferase, B-transferase, an inactive "O-transferase," or a pig alpha1-3galactosyltransferase (alpha1-3GT) synthesizing the Galalpha1-3Gal structure. The viruses were shown to carry the same ABO structures as the cells; that is, A but not B if produced in A-type cells, and B but not A if produced in B-type cells. Only O was detected on the virus produced from O-type cells, whereas reduced amounts of O appeared on the A- and B-type viral particles. In addition, the Galalpha1-3Gal structure was transferred onto measles only when grown in human cells expressing this structure. When subjected to human preimmune sera, the A-type, the B-type, and the Galalpha1-3Gal viral particles were partially neutralized in a complement-dependent manner. However, the O-type or the Galalpha1-3Gal-negative viral particles were not neutralized. The neutralization appeared to be mediated by specific NAb, as judged by specific inhibition using synthetic A and Galalpha1-3Gal oligosaccharides. Such viral glycosylation may thus partly explain why the ABO antigens and other similar intraspecies as well as interspecies polymorphic carbohydrates have evolved and been maintained over long evolutionary periods.

ABO Blood-Group System↗