Chromosomal defects in 34 male homosexuals, half of them with HIV antibodies

Abstract

Most of the research about viral interactions with human chromosomes was done during the sixties and early seventies and very few was performed after the human immunodeficiency virus (HIV) appearance as an epidemic in the eighties. The objective of this work was to estimate if particular chromosomal changes follow the infection of homosexual males by HIV and to determine if the lifestyle, habits, sexual practices, of our sample of male homosexuals predisposes them to chromosomal abnormalities at a higher rate than the background level of cytogenetic damage the general population has. This was a double blinded case-control study, 17 individuals positive for HIV antibodies (HIV+) detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blot (WB) were the cases, and 17 individuals negative for HIV antibodies (HIV-) the controls. These men were a very homogeneous population in terms of age, social status, lifestyles, drug abuse, sexual practices and education. Blood was collected between September 1988 and October 1989. Fresh whole blood was cultured in duplicate for 72 hr. Cell harvest followed conventional methods. Once all cell cultures were gathered, the tubes were picked up at random and air dried chromosome preparations were trypsin-giemsa banded (GTG) after overnight incubation at 60C'. The percentage of gaps and breaks these men had was not different from the reported for the general population, nor were there significant difference among both groups (O.R. = I .8) in terms of amount of chromosomal fragility. The distinction among them was at the level of the specific chromosomal sites where the gaps and breaks located, being sites at 2p21 and at 3p2I four times more frequent among HIV+. These probably represent viral modification sites on chromosomes which are known to look like non-staining gaps which are caused by the virus or viral products. This presumption is supported by an earlier report of repeated breaks at 3p21.1 , in fact this was the most common lesion site in this study of chromosomal aberrations of male homosexuals and the authors even considered the probability of "a new type of chromosome marker" . Furthermore, years later the CKR5 structural gene was mapped to human chromosome 3p21. This gene codes for the chemokine receptor 5 (CKR5) protein which serves as a secondary receptor on CD4+ T lymphocytes for certain strains of HIV-I. It is possible that this gene was being transcribed in HIV+ men and the consequent "staggering" of DNA contributed to the production of gaps and breaks at 3p21.En este estudio se determinaron las consecuencias citogenéticas de la infección con el virus de inmunodeficiencia humana (VIH), mediante un estudio tipo doble-ciego de casos infectados o VIH+ (N = 17) y controies VIH- (N = 17), en 34 hombres de una población muy homogénea de homosexuales, estudiada de 1988 a 1991. Se encontró fragilidad cromosómica no diferente del porcentaje informado de la población general ni diferente entre casos y controles (0.R. = 1.18). Las diferencias entre ambos grupos fueron más bien cualitativas, en los sitios de lesión cromosómica, ya que los hombres infectados mostraron cuatro veces más lesiones en dos genes en particular: 421 y 3p21. Este último coincidió con el sitio de fragilidad más común informado con anterioridad. Este sitio en 3p21 fue posteriormente identificado como el locus cromosómico donde se ubica el gen CKR5 el cual codifica para un receptor secundario en el linfocito T del VIH -1. Se propone que este gen se estaba transcribiendo activamente en los hombres infectados en los que se evidenciaron algunas fracturas cromosómicas en 3p21