Human Herpesvirus 6A Tegument Protein U14 Induces NF-κB Signaling by Interacting with p65

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Affinity precipitation. Affinity precipitation was performed as previously described (16, 60, 70). At

the indicated time point, either infected or transfected cells were lysed in buffer (50 mM Tris [pH 8.0],

0.1% NP-40, 150 mM NaCl) for 1 h at 4°C and then centrifuged at high speed. The supernatants of the

cell lysates were collected and incubated with Strep-Tactin beads (transfected cells) or protein GSepharose coupled with anti-U14 antibody (infected cells). These beads were rinsed with the same

buffer to remove unbound protein, and sample buffer containing 1,4-dithiothreitol (DTT) was added to

the beads. After boiling for 5 min, the samples were used for immunoblotting.

Separation of cellular fractions. Separation of cellular fractions was performed as previously

described (71). Briefly, cells were collected at the indicated times, rinsed with PBS, and lysed with hypotonic lysis buffer (10 mM HEPES [pH 7.5], 10 mM KCl, 3 mM MgCl2, 0.05% Nonidet P-40, 1 mM EDTA,

1 mM DTT, 10 mM NaF, 10 mM b -glycerophosphate, 0.1 mM sodium orthovanadate, protease inhibitor

mixture). The lysate was then incubated for 30 min prior to centrifugation at 500  g for 5 min at 4°C.

The supernatant was then transferred into fresh tubes as cytoplasmic fractions. The nuclear pellets were

rinsed twice in hypotonic lysis buffer containing increased amounts of Nonidet P-40 (0.1%) and lysed

with buffer containing 50 mM HEPES (pH 7.9), 250 mM KCl, 1% Nonidet P-40, 5% glycerol, 0.1 mM EDTA,

1 mM DTT, 10 mM NaF, 10 mM b -glycerophosphate, 0.1 mM sodium orthovanadate, and protease inhibitor mixture. The samples were frozen and thawed three times and incubated on ice for 30 min.

Insoluble material was pelleted at 14,000 rpm for 10 min at 4°C. The supernatant was then used as nuclear extracts. The lack of tubulin (cytoplasmic marker) and Lamin A/C (nuclear marker) were used as

controls for purity of the nuclear and cytoplasmic compartments, respectively.

Calculation of virus genome copy numbers. A total of 1  106 cells (JJhan) were infected with

U1102 in triplicate (1  105 genome copies/ml). At 24 h postinfection, infected cells were divided into

three aliquots. One aliquot was treated with 5 m M SC75741, another was treated with 10 m M QNZ, and

the remaining aliquot was kept untreated. At 72 h after infection, the infected cells were freeze-thawed,

DNA was extracted from the supernatant of the cells treated under each condition using the DNeasy

blood and tissue kit (Qiagen), and the genome copy number per milliliter of infected cell was quantitated by qPCR using SYBR Select master mix (Thermo Fisher Scientific). The sequence of primer used for

this purpose was 59-CGCTAGGTTGAGAATGATCGA-39 (forward) and 59-CAAAGCCAAATTATCCAGAGCG-39

(reverse) as described previously (72).

Statistical analysis. For the comparison of two groups, statistical analysis was performed using the

unpaired Student t test. Tukey’s test was used for multiple comparisons. A P value of .0.05 was considered not significant (n.s.).

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