Lipid droplets are essential cellular organelles for storage of fatty acids and triglycerides. The hepatitis C virus (HCV) translocates several of its proteins onto their surface and uses them for production of infectious progeny. We recently reported that the lipid droplet-associated α/β hydrolase domain-containing protein 5 (ABHD5/CGI-58) participates in HCV assembly by mobilizing lipid droplet-associated lipids. However, ABHD5 itself has no lipase activity and it remained unclear how ABHD5 mediates lipolysis critical for HCV assembly. Here, we identify adipose triglyceride lipase (ATGL) as ABHD5 effector and new host factor involved in the hepatic lipid droplet degradation as well as in HCV and lipoprotein morphogenesis. Modulation of ATGL protein expression and lipase activity controlled lipid droplet lipolysis and virus production. ABHD4 is a paralog of ABHD5 unable to activate ATGL or support HCV assembly and lipid droplet lipolysis. Grafting ABHD5 residues critical for activation of ATGL onto ABHD4 restored the interaction between lipase and co-lipase and bestowed the pro-viral and lipolytic functions onto the engineered protein. Congruently, mutation of the predicted ABHD5 protein interface to ATGL ablated ABHD5 functions in lipid droplet lipolysis and HCV assembly. Interestingly, minor alleles of ABHD5 and ATGL associated with neutral lipid storage diseases in human, are also impaired in lipid droplet lipolysis and their pro-viral functions. Collectively, these results show that ABHD5 cooperates with ATGL to mobilize triglycerides for HCV infectious virus production. Moreover, viral manipulation of lipid droplet homeostasis via the ABHD5-ATGL axis, akin to natural genetic variation in these proteins, emerges as a possible mechanism by which chronic HCV infection causes liver steatosis.

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Growth of colonies of the fungus Deuterophoma tracheiphila, the causal agent of the "mal secco" disease of lemons, is inhibited by two substances, C(1) and CS(2), which are found in resistant mandarin varieties but not in susceptible lemons and related species. Some properties of these substances are reported. CS(2) may be naringenin, but the stronger inhibitor, C(1), has not yet been identified.

Not long ago even some mycologists believed that fungi were c a p a b l e of world-wide spread without major hindrances." T h i s viewpoint w a s in direct contradiction t o findings made in higher plants by t h e c l a s s i c a l plant geographers, who had observed that their distribution w a s definitely governed by climatic and paleohistorical factors. It w a s my good fortune t o have been given an assignment by Adolph Engler, t h e well-known plant geographer of Berlin, Germany, t o help clarify t h i s obscure problem. T h i s work w a s carried out from 1917 t o 1920 on a large collection of fungi from Egypt assembled by G. Ehrenberg i n 1820. A taxonomic and biogeographic a n a l y s i s of t h e s e fungi demonstrated that Egyptian specimens identical with fungi of other countries shared similar climatic conditions. Conversely, where t h e climatic conditions of Egypt differed strongly from t h o s e in other countries, fundamental differences in t h e composition of t h e fungus flora were observed. T h i s Egyptian study offered conclusive evidence that spontaneous fungi a r e subject t o t h e same biogeographical l a w s as higher plants.T h i s study and my l a t e r s t u d i e s i n Palestine3" revealed that any biogeographical a n a l y s i s of all organisms cannot b e considered adequate u n l e s s approached from t h e following four viewpoints:(1) T h e distributional or geographical aspect: taking into account t h e mere occurrences without reference t o t h e environment. E a c h plant examined from t h i s point of view is called by us t h e organism's biogeographical or distributional "component."(2) T h e ecological aspect: bringing t h e plant into relationship with i t s environment. An examination from t h i s point of view presents t h e organism as an ecological or biogeographical "type."(3) T h e paleohistorical aspect: revealing t h e place of origin of t h e plant. Evaluated from t h i s angle, e a c h plant is termed t h e biogeographical "element." (4) T h e migratory aspect: tracing t h e routes t h e plant h a s followed during its migration. E a c h plant examined from t h i s viewpoint is classified a s a biogeographical "migrant."'This paper, illustrated with lantern slides, was presented at a meeting of the Division of Mycology on January 24, 1958.