Figure 2. The sterol regulatory complex promotes infection of ANDV.
(A) Infection of Chinese Hamster Ovary (CHO) cells null for S1P, S2P, or SCAP (Figure S2). CHO cells were infected with VSV-(G), rVSV-ANDV or rVSV-HTNV for 10 hours. Infections were quantified via flow cytometry and normalized relative to wild-type (CHO-K1) cells. Mean±SEM shown for three independent experiments; *** p<0.001. (Raw infection percentage (CHO-K1): VSV-(G) = 21%, rVSV-ANDV = 15%, VSV-(HTNV) = 8%) (B) siRNAs directed against SREBF2 efficiently knock down protein expression as measured by immunoblot to SREBP-2 with GAPDH as a loading control. (C) HEK293T cells depleted of SREBF2 were infected with non-replicating VSV pseudotypes bearing the indicated glycoproteins encoding red fluorescent protein (RFP) and infection was quantified 10 h.p.i.. Infectivity was normalized relative to control cells. Mean±SEM shown for three independent experiments; * p<0.05. (Raw infection percentage (control): VSV-(G) = 4%, VSV-(ANDV) = 19%, VSV-(HTNV) = 3%) (D) TALENs were used to genetically disrupt SCAP in HEK293T cells. These insertions were enriched upon challenge with rVSV-ANDV and were all killed by VSV-G. Enrichment was measured by a non-homologous end joining (NHEJ) endonuclease assay where a single band (top asterisk) indicates the presence of wild-type sequence and the lower molecular weight doublet (lower 2 asterisks) represents the disrupted alleles. Densitometry was used to quantify the levels of the undisrupted and disrupted alleles, which is shown below.
