Loss of cell membrane integrity during the acute phase of hantavirus infection. The level of LDH is plotted against time after onset of fever for the individual patients. uCat, units of catalytic activity.

Epithelial cell apoptosis is increased and correlates with the loss of cellular integrity during the acute phase of hantavirus infection. (A) Mean levels of the caspase-cleaved part of CK18 (M30) during the acute (530.2 ± 163.1 U/liter of caspase-cleaved CK18, ranging from 375.6 to 1,048.1 U/liter) and convalescent (386.7 ± 112.8 U/liter of caspase-cleaved CK18, ranging from 264.6 to 587.3 U/liter) phases of HFRS. Also shown are the mean levels of the non-caspase-cleaved part of CK18 (Non-M30) during the acute (391.9 ± 231.4 U/liter of non-caspase-cleaved CK18) and convalescent (411.9 ± 174.4 U/liter of non-caspase-cleaved CK18) phases and the total levels of CK18 (including both the caspase-cleaved and the non-caspase-cleaved forms of CK18) during the acute (922.1 ± 278.3 U/liter of total CK18) and convalescent (798.6 ± 253.6 U/liter of total CK18) phases. Data represent means ± standard deviations (n = 18). The mean proportion of caspase-cleaved CK18 out of total CK18 was 59.8% and 49.4% in acute and convalescent phases, respectively. (B) Individual levels of LDH plotted against caspase-cleaved CK18 during the acute phase of infection. The mean level of caspase-cleaved CK18 in a healthy population is 139 ± 82 U/liter (n = 118). uCat, units of catalytic activity.

Elevated levels of perforin and granzyme B in serum during the acute phase of hantavirus infection. Mean levels of extracellular perforin (A) and granzyme B (B) in serum at the acute (14.8 ± 6.0 ng perforin/ml, ranging from 6.5 to 26.2 ng/ml, and 265.0 ± 341.6 pg granzyme B/ml, ranging from 8.9 to 1,153.3 pg/ml, respectively) and convalescent (9.8 ± 3.1 ng perforin/ml, ranging from 5.4 to 15.0 ng/ml) phases of HFRS are shown. All but two samples were negative for granzyme B during the convalescent phase; the two positive samples had 4.4 and 13.3 pg granzyme B/ml, respectively. Data represent means ± standard deviations (n = 18). (C) Levels of perforin and granzyme B in serum for the acute-phase samples plotted against days after initial fever for the individual patients. (D) Levels of perforin plotted against the level of granzyme B in acute-phase serum from the individual patients. The serum levels of perforin and granzyme B in healthy subjects has been reported to be 8.0 ± 2.79 ng perforin/ml (15) and 11.5 pg granzyme B/ml (32), respectively.

Loss of cellular integrity correlates with the level of perforin during the acute phase of hantavirus infection. The individual levels of LDH were plotted against extracellular perforin during the acute phase of infection. uCat, units of catalytic activity.