Modulation of CD4, CXCR-4, and CCR-5 makes human hematopoietic progenitor cell lines infected with human herpesvirus-6 susceptible to human immunodeficiency virus type 1.
Two CD34+ human hematopoietic progenitor cell (HPC) lines, KG-1 and TF-1, became susceptible to human immunodeficiency virus type 1 (HIV-1) infection in the presence of a concurrent infection by human herpesvirus-6 (HHV-6). We have analyzed the possible mechanism(s) underlying this phenomenon in light of the recent demonstration that at least two members of the chemokine receptor family, CXCR4 (LESTR/fusin) and CCR5 molecules, are the HIV-1-specific coreceptors necessary, together with the high-affinity receptor CD4, for entry into target cells of T-tropic and M-tropic HIV-1 isolates, respectively. KG-1 cells show CXCR4 and CCR5 surface molecules in a large proportion of the cell population. Therefore, their susceptibility to both T-tropic and M-tropic HIV-1 strains, caused by HHV-6 infection, can be explained by the HHV-6-induced appearance of CD4 molecules in about 40% of the cell population. In TF-1 cells, 10%-15% of which are CD4+ and exhibit a consistent CCR5 presence in a large proportion of the cell population and a hardly detectable amount of CXCR4 in a very limited number of cells, HHV-6 infection does not modify the cell surface availability of HIV-1-specific high-affinity receptor or coreceptors.
Vignoli
M
M
Department of Clinical and Experimental Medicine of the University of Bologna, St Orsola General Hospital, Italy.
Furlini
G
G
Re
M C
MC
Ramazzotti
E
E
La Placa
M
M
D015704:CD4 Antigens / Q000096:biosynthesis* / Q000187:drug effects; D002460:Cell Line / Q000821:virology; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000209:etiology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000821:virology*; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology; D006801:Humans; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000187:drug effects; D013997:Time Factors; D014779:Virus Replication
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4