Abstract:
OBJECTIVES: Biological and genetic variability is a prominent feature of HIV strains especially in tropism, syncytial formation and replicative capacity. Preliminary studies also suggested host cell effects on HIV replication in monocytes. Therefore we used monocytes from identical/non-identical (IT/NIT) twins and age matched unrelated donors (URD) of the same sex to study host cell effects on HIV replication in monocytes. METHODS: HIV strains isolated in PBMC, were grown to high titre after 1-3 passages, ultracentrifuged and, aliquotted. Monocytes were purified by countercurrent elutriation and OKT3-complement cytotoxicity. HIV replication in monocytes was studied under identical conditions in sextuplicate with equal input multiplicities of 10(6) TCID50/ml. Supernatants were aspirated for HIV antigen assay (at 2, 4, 7, 12 and 16 days) and in situ hybridisation at day 7. All HIV antigen assays were conducted simultaneously with quantitative controls (Abbott). Identity or non-identity of twins (Australian NHMRC Twin Registry) was confirmed by history, phenotype, blood group, red cell isoenzymes, HLA typing and restriction fragment length polymorphisms. RESULTS: Replication of 4 different HIV strains in monocytes from four pairs of IT, 2 pairs of NIT and 3 pairs of URD showed kinetic curves characteristic of high or low replicating viruses. The curves in the IT monocytes were insignificantly different within pairs, but in the URD monocytes marked and significant differences occurred within pairs ie high replicating HIV strains in one were low replicating in the URD monocyte pair (p = less than 0.02 for each pair). No significant differences were observed with monocytes from serial bleeds of the same donor. HIV replication in NID monocytes showed intermediate patterns: viral kinetic curves in some paired monocytes were almost identical whereas in other pairs of non-identical twins three were marked differences. Their typing is in progress. CONCLUSIONS: Marked and significant differences in HIV replication kinetics between URD monocyte pairs contrasted with congruent patterns in ID monocytes and strongly suggested a host cell influence on HIV replication in monocytes.
Keywords: Cells, Cultured Comparative Study Disease Susceptibility/GENETICS Female Human HIV/*PHYSIOLOGY Leukocytes, Mononuclear/*MICROBIOLOGY Male *Twins, Dizygotic *Twins, Monozygotic Variation (Genetics) *Virus Replication ABSTRACT 921230
M92C4890
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
