BLOOD MONOCYTES INFECTED IN-VIVO BY HIV-1 VARIANTS WITH A SYNCYTIUM-INDUCING PHENOTYPE

Extensive data have been obtained on sequence changes in the V3 region of the HIV-1 envelope protein that are associated with in vitro biolo gical properties such as cell tropism and syncytium-inducing capacity. However, so far this concerned viruses isolated from peripheral blood mononuclear cells and thus did not discriminate between variants pres ent in T lymphocytes or in monocytes. In this study, we analyzed viral sequences derived separately from uncultured T lymphocytes, blood mon ocytes, and plasma of an HIV-1-infected patient showing a neurological evolution of the disease. Sequences related to the V3 region and 18 a mino acids downstream were obtained from 48 clones after PCR amplifica tion. One predominant viral sequence close to the monocytotropic/non-s yncytium-inducing (NSI) consensus sequence was observed in the three b lood sources. Two viral species were specifically identified in monocy tes (43% of the clones), showing clear differences from the consensus sequence and exhibiting the genetic determinants associated with the S I phenotype. Plasma-derived viruses with a similar V3 loop were obtain ed on in vitro isolation. Analysis of the biological properties of the se selected viruses confirmed their monocytotropism and the syncytium- inducing phenotype as expected by the cell type in which the sequences were observed and the charge of the V3 loop. Structural analysis of t hese variants suggested an intermediate structure between NSI/monocyto tropic and SL/lymphotropic V3 loops. Thus, in vivo circulating monocyt es could be a reservoir for distinct HIV-1 variants with potential SI characteristics, at least in later stages of infection. Studying such variants over the course of the infection may shed light on their invo lvement in disease manifestations.