Productive Infection of Primary Macrophages with Human Herpesvirus 7

Abstract

Here we demonstrate replication of human herpesvirus 7 (HHV-7), a T-lymphotropic virus, in macrophages. Productive replication was lost after 2 weeks, but HHV-7 DNA was detected up to 1 month after infection. Thus, macrophages become infected by HHV-7 and might play an important role as a viral reservoir, as has been demonstrated for human immunodeficiency virus type 1.Human herpesvirus 7 (HHV-7) was first isolated in 1990 from peripheral blood mononuclear cells (PBMC), under conditions required to promote T-cell activation, from a healthy individual and later on also from a patient with chronic fatigue syndrome (3, 5). HHV-7 utilizes CD4 as its main receptor to enter the target cell and has also been shown to interfere with human immunodeficiency virus type 1 infection in CD4 ϩ T cells (6, 11). So far, only CD4 ϩ T lymphocytes (isolated from PBMC and cord blood mononuclear cells) and SupT1 cells, immature T-cells derived from a non-Hodgkin's lymphoma, have proved sensitive to HHV-7 infection (2, 12). Lack of productive HHV-7 infection in CD4 ϩ macrophages was observed by quantitative PCR and immunofluorescence assays to detect HHV-7 antigen in vitro (4). It has also been demonstrated that HHV-7 antigen is expressed in macrophages/ monocytes of AIDS-associated Kaposi's sarcoma samples (8). Another, more recent study has shown that in lymph nodes of AIDS patients HHV-7 is mainly present in macrophages (9). This suggests that macrophages can be infected with HHV-7 and may be a site of latency and reactivation of HHV-7 in vivo.In the present study, we evaluated HHV-7 infection of macrophages in vitro. Our results suggest that HHV-7 can infect macrophages and that this infection may persist in these cells for a long time. Macrophages were isolated by density gradient centrifugation from PBMC from healthy blood donors and further enriched, as described in detail elsewhere (1). More than 99% of the cells were CD14 ϩ CD4 ϩ CD3 Ϫ , and no HHV-7 DNA was detected by PCR in these cell cultures. The stock of HHV-7 (strain KHR) was grown in CD8-depleted PBMC, as described previously (13). The CD4 ϩ T-cell line SupT1, the CD4 Ϫ cell line HSB-2, the CD4 ϩ cell line MT-2, and the monocytic CD4ϩ THP-1 cell line were purchased from the American Type Culture Collection (Rockville, Md.).To study the HHV-7 infection in macrophages, the cells were inoculated with virus stock for 4 h and then extensively washed. The SupT1, HSB-2, MT-2, and THP-1 cell lines were also used to determine HHV-7 infection. The mock-infected and HHV-7-infected macrophage cultures were evaluated regularly by light microscopy. PCR, reverse transcription (RT)-PCR, and electron microscopy were also used to detect HHV-7 DNA, mRNA, and HHV-7 particles.DNA was isolated from mock-infected and HHV-7-infected macrophages at different time points after HHV-7 infection. Briefly, the cells were washed extensively with phosphate-buffered saline and collected, and total DNA of the cell pellet was isolated using QIAamp DNA blood Mini Kit (Qiagen, Hilden, Germany) following ...

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