Table 1.
Organ-specific cell types contributing to orthohantavirus disease in vivo summarized for five major organs.
| Affected organ | Infected cell type | HFRS | HCPS | Hypothesis on pathology | References | ||
|---|---|---|---|---|---|---|---|
| Human | Reservoir | Human | Reservoir | ||||
| Lungs | Pulmonary microvascular endothelium | + | + | + | + | Extensive infection leads to immune cell infiltrations and endothelial cell activation, which causes local inflammation and pulmonary edema | Brummer-Korvenkontio et al., 1980; Lee et al., 1981, 1982; Gavrilovskaya et al., 1983; LeDuc et al., 1984; Yanagihara et al., 1985; Nolte et al., 1995; Zaki et al., 1995; Green et al., 1998; Toro et al., 1998; Netski et al., 1999; Padula et al., 2004; Easterbrook and Klein, 2008b; Rasmuson et al., 2011; Clement et al., 2014 |
| Heart | Myocardial endothelium | – | ? | + | + | Infection leads to immune cell infiltrations and endothelial cell activation, causing interstitial edema that contributes to myocardial dysfunction and cardiogenic shock | Nolte et al., 1995; Zaki et al., 1995; Green et al., 1998; Botten et al., 2002; Hautala et al., 2002; Saggioro et al., 2007; Michalski et al., 2014; Dervovic and Hukic, 2016 |
| Kidneys | Tubular epithelium | + | +* | – | ? | Infection of endothelium leads to immune cell infiltrations (tubulointerstitial nephritis) with redistribution of tight junction proteins, along with direct tubular necrosis (with possible interstitial hemorrhages) causing functional impairment of tubuli leading to proteinuria, microscopic hematuria | Hung et al., 1992; Kim et al., 1993; Groen et al., 1996; Green et al., 1998; Botten et al., 2002; Hautala et al., 2002; Krautkramer et al., 2011 |
| Glomerular endothelium | + | +* | + | + | Infection of glomeruli causes decrease in glomerular ZO-1 expression relating to reduced function of the glomerulus as molecular filter by enhancing glomerular permeability, leading to proteinuria and microscopic hematuria | Zaki et al., 1995; Groen et al., 1996; Green et al., 1998; Netski et al., 1999; Botten et al., 2002; Krautkramer et al., 2013 | |
| Liver | Hepatic sinusoidal endothelium | ? | + | + | + | Infection of endothelium leads to immune cell infiltrations (antigen-positive Kupffer cells) and increased vascular permeability, which probably do not lead to significant liver dysfunction as hepatic sinusoidal microvasculature is already relatively permeable | Gavrilovskaya et al., 1983; Yanagihara et al., 1985; Zaki et al., 1995; Green et al., 1998; Toro et al., 1998; Netski et al., 1999 |
| Spleen | Splenic sinusoidal endothelium | + | + | + | +* | Infection of immune cells in the spleen may cause over-activation of immature lymphocytes elsewhere and facilitate prolonged virus dissemination throughout the body | Lee et al., 1982; Gavrilovskaya et al., 1983; LeDuc et al., 1984; Yanagihara et al., 1985; Zaki et al., 1995; Green et al., 1998; Netski et al., 1999; Hautala et al., 2002; Klingstrom et al., 2002; Compton et al., 2004; Padula et al., 2004; Sironen et al., 2008, 2017; Michalski et al., 2014 |
Viral antigen presence in mononuclear immune cells are not included in table. + = viral antigen present of at least one causative virus species, ? = conflicting data/not tested, – = viral antigen absent of all tested causative virus species, and * = studies did not specify infected cell type within organ.