SARS-coronavirus replication in human peripheral monocytes/macrophages

Abstract

A novel coronavirus (CoV) has been described in association with cases of severe acute respiratory syndrome (SARS). The virus, SARS-CoV, differs from the previously described human coronaviruses, 229E and OC43. 229E was previously shown to productively infect human monocytes/macrophages, whereas OC43 poorly infected the cells. In this study, we examined whether SARS-CoV could productively infect purified monocytes/macrophages (PM) derived from human donor cells. Unlike 229E-infected cells, which produced viral titers of 10(3.5) to 10(6)TCID50/ml, SARS-CoV replicated poorly in PM, producing titers of 10(1.75) to 10(2)TCID50/ml. This finding was similar to results reported for OC43-infected cells, with titers ranging from 10(1.2) to 10(2.7)TCID50/ml. Of interest, SARS-CoV proteins were detected only in PM that did not produce significant amounts of interferon (IFN)-alpha, and in one such case, preliminary electron microscope studies demonstrated that SARS-CoV-like particles could enter the cells, possibly via phagocytosis. These results suggest that SARS-CoV, like human CoV OC43, poorly infects human PM, and production of IFN-alpha by these cells further limits the infection. Given the importance of monocytes/macrophages to the immune response, it is possible that their infection by SARS-CoV and alteration of this infection by IFN-alpha may be important to the course of the infection in humans.

Activation of human monocytes after infection by human coronavirus 229E

“…The detection of HCoV-OC43 RNA in primary monocytes/macrophages (data not shown) is consistent with these cells participating in virus dissemination, as suggested for SARS-CoV (Yilla et al, 2005). However, infectious HCoV-OC43 particles were not detected as early as 24 hpi postinfection, suggesting that viral RNA detected at 48 hpi represents non-infectious virus, still cell-associated.…”

Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection

“…17e19 The pulmonary tissues of SARS patients were also well characterized by pronounced infiltration of monocytes and macrophages. 17,31,32 Furthermore, SARS-CoV was shown to infect the monocyte-derived macrophages in vitro 15,33 and, to be readily detectable in macrophages in lungs and other target organs of SARS patients. 31,32 Based on these observations, Gu et al have argued that the SARS virus infects resident, infiltrating, and circulating immune cells, such as macrophages and monocytes; and then, these infected circulating cells may carry SARS-CoV to various target organs as manifested by widespread dissemination.…”

Up-regulation of IL-6 and TNF-α induced by SARS-coronavirus spike protein in murine macrophages via NF-κB pathway

“…Angiotensin-converting enzyme 2 (ACE2) has been identified as a functional receptor for SARS-CoV, and the tissue distribution of ACE2 has been studied extensively (Hamming et al, 2004;To and Lo, 2004). Although immune cells lack ACE2, SARS-CoV can infect human macrophages and dedritic cells Tseng et al, 2005;Yilla et al, 2005) without producing infectious virus particles, suggesting that SARS-CoV can entry the immune cells via other receptors. Toll-like receptors (TLRs), a major class of molecular pattern recognition receptors, are activated by direct interaction of the extracellular domain of the receptor with a pathogen-associated molecular pattern, resulting in activation of NF-B, IRF3, and MAPK singaling pathways.…”