Human cytomegalovirus modulation of CCR5 expression on myeloid cells affects susceptibility to human immunodeficiency virus type 1 infection

Abstract

For some time there has been evidence suggesting an interaction between human cytomegalovirus (HCMV) and Human immunodeficiency virus (HIV) in the pathogenesis of AIDS. Here, the interaction of HCMV and HIV-1 was examined in monocyte/macrophage cells, two cell types known to be targets for both viruses in vivo. Infection experiments demonstrated that prior infection with HCMV impeded subsequent superinfection with HIV-1. In contrast, uninfected bystander cells within the population were still permissive for HIV-1 infection and were also found to express increased levels of Gag after HIV-1 superinfection. Analysis of CCR5, a co-receptor for HIV-1, on HCMV-infected and bystander cells showed a substantial loss of surface CCR5 expression on infected cells due to HCMV-induced reduction of total cellular CCR5. In contrast, uninfected bystander cells displayed increased surface CCR5 expression. Furthermore, the data suggested that soluble factor(s) secreted from HCMV-infected cells were responsible for the observed upregulation of CCR5 on uninfected bystander cells. Taken together, these results suggest that, whilst HCMV-infected monocytes/macrophages are refractory to infection with HIV-1, HCMV-uninfected bystander cells within a population are more susceptible to HIV-1 infection. On this basis, HCMV infection may contribute to the pathogenesis of HIV-1.

Human CMV Infection of Porcine Endothelial Cells Increases Adhesion Receptor Expression and Human Leukocyte Recruitment

“…However, although porcine IL-8 binds human leukocytes, its potential effect on human leukocyte chemotaxis is a matter of debate (57,58). Together with previous studies, our data stress the importance of soluble factors released from infected cells that contribute to an amplification of the immune and inflammatory response (15,16,59,60). Furthermore, HCMV induced apoptosis in HCMV-infected pEC cultures (Millard, unpublished data).…”

C‐Reactive Protein Mediates the Effect of Apolipoprotein E on Cytomegalovirus Infection

“…It is related to numerous conditions in this group, including ocular CMV disease, immune reconstitution syndrome, gastrointestinal disease, encephalitis and pneumonia, and mortality [36]. Furthermore, there is increasing evidence of an association between the presence of 4 and enhanced risk of HIV-related dementia [3,37,38]. Our results suggest that 4 is a factor that influences CMV IgG antibody levels.…”

Association of Host Genetic Risk Factors With the Course of Cytomegalovirus Retinitis in Patients Infected With Human Immunodeficiency Virus

“…Moreover, CMV can activate HIV latent provirus,45 alter the tropism of HIV,46 encode an alternative receptor for HIV,47 and act as a cofactor enhancing progression of AIDS even in the era of HAART 10, 48. Yet, a recent observation showed that CMV- infected cells can secrete soluble factors that are able to increase CCR5 surface expression on uninfected bystander cells 49. One can speculate that the CCR5 +.p1.+ promoter haplotype associated with increased CCR5 expression may be upregulated further due to CMV activation, making immune cells more susceptible to HIV-1 infection.…”