INFLUENZA VIRUS ALTERS HEPATIC MITOCHONDRIAL OXYGEN CONSUMPTION UTILIZING ELECTRON TRANSFERRING DYES IN A MOUSE MODEL OF REYE'S SYNDROME

Abstract

Influenza B virus given i.v. to mice results in leakage of hepatic mitochondrial (HM) enzymes into the cytoplasm (Biochem Med 28:109, 1982) suggesting that the virus may alter HM membrane permeability and function. Accordingly, studies of oxidative phosphorylation were performed in HM obtained from 4-6 week old male Balb C mice given 12, 800 hemagglutination units of egg-grown Influenza B Lee/40 virus (V) or vehicle (C) i.v. and studied 36 hours later. When the substrates glutamate (G), succinate (S), and ascorbate (A) were utilized, States 3 and 4 oxygen consumption did not differ between V and C. However the ADP:0 ratio for G was decreased in V (2.88) vs. C 3.01-p<0.023), perhaps secondary to viral activation of endogenous ATPase with resultant recycling of ADP. TMPD (tetramethylenephenylene diamine) and PMS (phenazine methosulfate) are electron transferring cationic and anionic dyes respectively. Mitochondria with decreased fixed negative charge are more permeable to anions. PMS supported respiration (2.85 ng atoms O/min/mg protein) in V vs. 0.0 for C-p<0.004. In contrast TMPD sustained greater O2 consumption in C (14.17 ng atoms O/min/ mg protein) than in V-9.80) when employed alone (p<0.056) or with antimycin A + glutamate (11.62 for C vs. 5.45 for V) (p<0.011). The above data suggest that Influenza virus may alter HM permeability and fixed negative charge but does not impair respiratory function.