DNA and protein heterogeneity in serial isolates of human immunodeficiency virus (HIV-1): indication of change in vivo

Abstract

Structural heterogeneity in human immunodeficiency virus (HIV-1) isolates from different sources has been reported. In order to investigate if the virus exhibits heterogeneity in vivo, HIV-1 was isolated over a 3 year period (1983-1985) from a blood donor who progressed from the asymptomatic carrier state to frank AIDS. The HIV-1 specific proteins were characterized and compared by metabolic labelling and immunoprecipitation of infected cells and by Western blot analysis of gradient purified isolates. The data indicate polymorphism in the apparent size of gag gene-encoded p55 and env gene-encoded p41 proteins. The possibility of genomic variations was evaluated by studying the restriction enzyme polymorphism of integrated proviral DNA. Genetic diversity between 1983, 1984 and 1985 isolates was demonstrated by a change in the number and/or size of restriction fragments. In addition, genetic variation was also observed in HIV-1 isolated from the blood transfusion recipient of this donor. Subsequent analysis of the quantitative and qualitative titre of HIV-1 specific antibodies in the donor recipient sera demonstrated a concomitant change with the observed structural variation in the virus. These studies may be useful in elucidating virus or host-related critical events which lead to the onset of AIDS following infection with HIV-1.