TABLE 6.
Tissue and host tropism of MERS-CoV demonstrated in cell culture systemsa
| Cell culture system | Anatomic site or animal species | Main findingsb | Reference |
|---|---|---|---|
| Cell lines | |||
| Human cell types | |||
| Lower respiratory tract | |||
| A549 | Lung adenocarcinoma | Replication with increased viral load (∼1–2), N protein expression, and CPE | 116 |
| Calu-3 | Polarized bronchial epithelium | Replication with increased viral load (∼4–5), N protein expression, and CPE (cell rounding, detachment, and prominent syncytium formation) | 116 |
| Replication in Calu-3 cells with increased viral load (∼5–6) and CPE at 24 hpi; infection and release of virions through both the apical and basolateral routes | 184 | ||
| HFL | Embryonic lung fibroblasts | Replication with increased viral load (∼4–5), N protein expression, and CPE | 116 |
| Differentiated HTBE | Human tracheobronchial epithelium | Replication with increased viral load (∼2.5–4.5) in differentiated HTBE cells; virions released exclusively from the apical and not from the basolateral side | 185 |
| Nondifferentiated HTBE | Human tracheobronchial epithelium | Replication with increased viral load (<1) in nondifferentiated but much less than that observed in differentiated HTBE cells | 185 |
| HAE | Pseudostratified human airway epithelium | Productive infection in HAE cultures peaks at 48 hpi: host cell factors required for cell entry, RNA synthesis, and virus assembly and release are available in human | 186 |
| Replication in HAE, lung fibroblasts, type II pneumocytes, and microvascular endothelial cells; most efficient in HAE and lung fibroblasts | 187 | ||
| HBEpC | Human primary bronchial epithelium | Replication with increased viral load (∼0.5–1) (∼1,000-fold-lower concentrations of virus progeny than in HREpC) and without CPE | 157 |
| Kidney | |||
| HEK 293 | Human embryonic kidney | Replication with increased viral load (∼4–5), N protein expression, and CPE | 116 |
| 769-P | Renal cell adenocarcinoma | Replication with increased viral load (∼3–4) | 117 |
| HREpC | Human primary kidney epithelium | Replication with increased viral load (∼3–4) (∼1,000-fold-higher concentrations of virus progeny than in HBEpC) and CPE (rounding and detachment of cells with cell death in the majority of cells after only 20 hpi) | 157 |
| Colon | |||
| Caco-2 | Colorectal adenocarcinoma | Replication with increased viral load (∼4–5), N protein expression, and CPE (cell rounding, detachment, and prominent syncytium formation) | 116 |
| LoVo | Metastatic colonic adenocarcinoma | Replication in LoVo cells with increased viral load (∼5–6) and CPE at 4 days p.i. | 184 |
| Liver | |||
| Huh-7 | Hepatocellular carcinoma | Replication with increased viral load (∼4–5), N protein expression and CPE (cell aggregates with marked shrinkage) | 116 |
| Neuromuscular | |||
| NT2 | Neurocommitted teratocarcinoma | Replication with increased viral load (∼2–3) but no N protein expression and CPE | 116 |
| Immune | |||
| THP-1 | Peripheral blood monocytes from AML | Replication with increased viral load (<1) but no N protein expression and CPE | 116 |
| U937 | Monocytes from histiocytic lymphoma | Replication with increased viral load (<0.5) but no N protein expression and CPE | 116 |
| H9 | T lymphocytes from T-cell leukemia | Replication with increased viral load (<0.5) but no N protein expression and CPE. | 116 |
| Jurkat_CD26DPP4+ | Human T lymphocytes transfected with a human DPP4-encoding plasmid | Conversion from nonsusceptible state to susceptible state with productive viral infection after plasmid transfection | 184 |
| His-1 | Malignant histiocytoma | Replication with increased viral load (∼3–4), N protein expression, and CPE | 116 |
| Nonhuman cell types | |||
| Primates | |||
| LLC-MK2 | Rhesus monkey kidney | Replication with increased viral load (∼4–5), N protein expression, and CPE | 116 |
| Vero | African green monkey kidney | Replication with increased viral load (∼4–5), N protein expression, and CPE | 116 |
| Vero-TMPRSS2 | African green monkey kidney cells expressing TMPRSS2 | Early appearance of large syncytia at18 hpi and virus particle-induced cell-cell fusion at 3 hpi | 52 |
| Vero E6 | African green monkey kidney | Replication with increased viral load (∼4–5) and N protein expression; slower and less obvious CPE than in Vero cells | 58, 116 |
| COS-7 with DPP4 | African green monkey fibroblasts transfected with a human DPP4-encoding plasmid | Conversion from nonsusceptible state to susceptible state with productive viral infection after plasmid transfection | 46 |
| Bats | |||
| RoNi/7 | Old World bat (Rousettus aegyptiacus) kidney | Replication with increased viral load (∼3–4) | 117 |
| PipNi/1 | Old World bat (Pipistrellus pipistrellus) kidney | Replication with increased viral load (∼1–2) | 117 |
| PipNi/3 | Old World bat (Pipistrellus pipistrellus) kidney | Replication with increased viral load (∼1–2) | 117 |
| RhiLu | Old World bat (Rhinolophus landeri) lung | Replication with increased viral load (∼2–3) | 117 |
| MyDauNi/2 | Old World bat (Myotis daubentonii) kidney | Replication with increased viral load (∼1–2) | 117 |
| CarNi/1 | New World bat (Carollia perspicillata) kidney | Replication with increased viral load (<0.5) | 117 |
| EFF | New World bat (Eptesicus fuscus) embryo | Susceptible to MERS-CoV pseudovirus infection | 23 |
| EidNi/41.3 | Old World bat (Eidolon helvum) adult kidney | Replication with increased viral load (∼106 PFU/ml) | 319 |
| EpoNi/22.1 | Old World bat (Epomops buettikoferi) adult kidney | Replication with increased viral load (∼104 PFU/ml) | 319 |
| HypLu/45.1 | Old World bat (Hypsignathus monstrosus) fetal lung | Replication with increased viral load (∼105 PFU/ml) | 319 |
| HypNi/1.1 | Old World bat (Hypsignathus monstrosus) fetal kidney | Replication with increased viral load (∼105 PFU/ml) | 319 |
| PESU-B5L | New World bat (Pipistrellus subflavus) adult lung | Did not support productive MERS-CoV infection unless transfected with a plasmid expressing human DPP4 | 319 |
| RO5T | Old World bat (Rousettus aegyptiacus) embryo | Did not support productive MERS-CoV infection unless transfected with a plasmid expressing human DPP4 | 319 |
| RO6E | Old World bat (Rousettus aegyptiacus) embryo | Did not support productive MERS-CoV infection unless transfected with a plasmid expressing human DPP4 | 319 |
| RoNi/7.1 | Old World bat (Rousettus aegyptiacus) adult kidney | Replication with increased viral load (∼106 PFU/ml) | 319 |
| RoNi/7.2 | Old World bat (Rousettus aegyptiacus) adult kidney | Replication with increased viral load (∼106 PFU/ml) | 319 |
| Tb1Lu | New World bat (Tadarida brasiliensis) adult lung | Did not support productive MERS-CoV infection unless transfected with a plasmid expressing human DPP4 | 319 |
| Camelids | |||
| TT-R.B | Arabian camel (Camelus dromedarius) umbilical cord | Replication with increased viral load (∼1) but without production of infectious virus particles | 118 |
| LGK-1-R | Alpaca (Llama pacos) kidney | Replication with increased viral load (∼2–3) and production of infectious virus particles | 118 |
| Other mammals | |||
| ZLu-R | Goat (Capra hircus) lung | Replication with increased viral load (∼1–2) and production of infectious virus particles | 118 |
| ZN-R | Goat (Capra hircus) kidney | Replication with increased viral load (∼3–4) and production of infectious virus particles | 118 |
| PK-15 | Pig kidney | Replication with increased viral load (∼4–5), N protein expression, and CPE | 116 |
| PS | Pig kidney | Replication with increased viral load (<1) | 117 |
| RK-13 | Rabbit kidney | Replication with increased viral load (∼1–2) but no N protein expression and CPE | 116 |
| CL-1 | Civet lung fibroblasts | Replication with increased viral load (∼1–2), N protein expression, and CPE | 116 |
| PN-R | Horse kidney | Replication with production of infectious virus progeny, increased viral load (∼7–8), and CPE | 336 |
| PFN-R | Horse kidney | Replication with production of infectious virus progeny, increased viral load (∼7–8), and CPE | 336 |
| MDCK with human DPP4 | Dog kidney transfected with a human DPP4-encoding plasmid | Conversion from nonsusceptible state to susceptible state with productive viral infection after plasmid transfection | 46 |
| LR7 with human DPP4 | Mouse fibroblasts transfected with a human DPP4-encoding plasmid | Conversion from nonsusceptible state to susceptible state with productive viral infection after plasmid transfection | 46 |
| CRFK with human DPP4 | Cat kidney cortex epithelium transfected with a human DPP4-encoding plasmid | Conversion from nonsusceptible state to susceptible state with productive viral infection after plasmid transfection | 46 |
| BHK with human DPP4 | Baby hamster kidney cells expressing human DPP4 | Conversion from nonsusceptible state to susceptible state after transfection with a human but not hamster or ferret DPP4-encoding expression vector | 48 |
| Primary ferret kidney with human DPP4 | Primary ferret kidney cells expressing human DPP4 | Conversion from nonsusceptible state to susceptible state with after transfection with a human but not hamster or ferret DPP4-encoding expression vector | 48 |
| Ex vivo organ or cell cultures | |||
| Respiratory tract | |||
| Lower respiratory tract | Human lung | Infection and replication in most cell types of the human alveolar compartment (ciliated and nonciliated cells in simple columnar and simple bronchial epithelia, type I and II pneumocytes, endothelial cells of large and small pulmonary vessels, but not alveolar macrophages) | 188 |
| Human bronchus and lung | Productive replication in both human bronchial and lung ex vivo organ cultures (nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells); virions were found within the cytoplasm of bronchial epithelial cells, and budding virions were found in alveolar epithelial cells (type II) | 189 | |
| Human lung | Infection of airway epithelial cells (pneumocytes and epithelial cells of terminal bronchioles, endothelial cells, and lung macrophages) | 190 | |
| Human bronchus and lung | The respiratory tropisms of human and dromedary MERS-CoV strains in ex vivo human bronchus and lung culture were similar | 338 | |
| Immune cells | |||
| Peripheral blood mononuclear cells | Human MDMs | Productive infection and replication in MDMs with increased viral load (∼3–4) and aberrant induction of inflammatory cytokines and chemokines (higher expression levels of IL-12, IFN-γ, IP-10, MCP-1, MIP-1α, IL-8, CCL-5, MHC class I, and costimulatory molecules than SARS-CoV-infected MDMs) | 190 |
| Human MoDCs | Productive infection of MoDCs with increased viral load (∼2–3) and significantly higher expression levels of inflammatory cytokines and chemokines (IL-12, IFN-γ, IP-10, CCL-5, MHC class II, and the costimulatory molecule CD86) than SARS-CoV-infected MoDCs | 192 |
a
Abbreviations: AML, acute monocytic leukemia; CCL, chemokine C-C motif ligand; CPE, cytopathic effects; p.i., postinfection; hpi, hours postinfection; IFN, interferon; IL, interleukin; IP, interferon-γ-induced protein; MCP, monocyte chemotactic protein; MDM, monocyte-derived macrophage; MHC, major histocompatibility complex; MIP, macrophage inflammatory protein; MoDC, monocyte-derived dendritic cell; N, nucleocapsid; TMPRSS2, transmembrane protease serine protease 2.
b
Values of viral loads are presented as log10 virus RNA genome copies equivalents per ml of cell culture supernatant unless otherwise specified.