A cytotoxicity test protocol for single-wall nanotubes (SWNTs), multi-wall nanotubes (with diameters ranging from 10 to 20 nm, MWNT10), and fullerene (C60) was tested. Profound cytotoxicity of SWNTs was observed in alveolar macrophage (AM) after a 6-h exposure in vitro. The cytotoxicity increases by as high as approximately 35% when the dosage of SWNTs was increased by 11.30 microg/cm2. No significant toxicity was observed for C60 up to a dose of 226.00 microg/cm2. The cytotoxicity apparently follows a sequence order on a mass basis: SWNTs > MWNT10 > quartz > C60. SWNTs significantly impaired phagocytosis of AM at the low dose of 0.38 microg/cm2, whereas MWNT10 and C60 induced injury only at the high dose of 3.06 microg/cm2. The macrophages exposed to SWNTs or MWNT10 of 3.06 microg/cm2 showed characteristic features of necrosis and degeneration. A sign of apoptotic cell death likely existed. Carbon nanomaterials with different geometric structures exhibit quite different cytotoxicity and bioactivity in vitro, although they may not be accurately reflected in the comparative toxicity in vivo.

We have previously shown that Toll-like receptor (TLR)-activated murine nonparenchymal liver cells [(NPC); Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC)]T he hepatitis B virus (HBV) is a hepatotropic DNA virus that can lead to chronic hepatitis, which can be complicated by the development of liver cirrhosis and hepatocellular carcinoma. Current approved therapeutic strategies for treatment HBV include interferon-alpha (IFN-␣) and nucleoside and nucleotide analogs. 1,2 However, only a minority of patients that are treated with these agents show a long-term sustained response with "eradication" [for example, hepatitis B surface antigen (HBsAg) loss] of the virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 pandemic. How SARS-CoV-2 regulates cellular responses to escape clearance by host cells is unknown. Autophagy is an intracellular lysosomal degradation pathway for the clearance of various cargoes, including viruses. Here, we systematically screened 28 viral proteins of SARS-CoV-2 and identified that ORF3a strongly inhibited autophagic flux by blocking the fusion of autophagosomes with lysosomes. ORF3a colocalized with lysosomes and interacted with VPS39, a component of the homotypic fusion and protein sorting (HOPS) complex. The ORF3a–VPS39 interaction prohibited the binding of HOPS with RAB7, which prevented the assembly of fusion machinery, leading to the accumulation of unfused autophagosomes. These results indicated the potential mechanism by which SARS-CoV-2 escapes degradation; that is, the virus interferes with autophagosome–lysosome fusion. Furthermore, our findings will facilitate strategies targeting autophagy for conferring potential protection against the spread of SARS-CoV-2.