0	6	Potent	potent	JJ
7	10	and	and	CC
11	17	stable	stable	JJ
18	29	attenuation	attenuation	NN
30	32	of	of	IN
33	43	live-HIV-1	live-hiv-1	NN
44	46	by	by	IN
47	51	gain	gain	NN
52	54	of	of	IN
55	56	a	a	DT
57	78	proteolysis-resistant	proteolysis-resistant	JJ
79	88	inhibitor	inhibitor	NN
89	91	of	of	IN
92	101	NF-kappaB	NF-kappaB	NNP
102	103	(	(	(
103	123	IkappaB-alphaS32/36A	IkappaB-alphaS32/36A	NNP
123	124	)	)	)
125	128	and	and	CC
129	132	the	the	DT
133	145	implications	implication	NNS
146	149	for	for	IN
150	157	vaccine	vaccine	NN
158	169	development	development	NN
169	170	.	.	.

172	187	Live-attenuated	live-attenuated	JJ
188	193	human	human	JJ
194	210	immunodeficiency	immunodeficiency	NN
211	218	viruses	virus	NNS
219	220	(	(	(
220	224	HIVs	HIV	NNPS
224	225	)	)	)
226	229	are	be	VBP
230	240	candidates	candidate	NNS
241	244	for	for	IN
245	253	Acquired	acquire	VBN
254	270	Immunodeficiency	Immunodeficiency	NNP
271	279	Syndrome	Syndrome	NNP
280	281	(	(	(
281	285	AIDS	AIDS	NNP
285	286	)	)	)
287	294	vaccine	vaccine	NN
294	295	.	.	.

296	301	Based	base	VBN
302	304	on	on	IN
305	308	the	the	DT
309	315	simian	simian	JJ
316	332	immunodeficiency	immunodeficiency	NN
333	338	virus	virus	NN
339	340	(	(	(
340	343	SIV	SIV	NNP
343	344	)	)	)
345	350	model	model	NN
351	354	for	for	IN
355	359	AIDS	AIDS	NNP
359	360	,	,	,
361	377	loss-of-function	loss-of-function	NN
378	379	(	(	(
379	383	e.g.	e.g.	FW
384	392	deletion	deletion	NN
393	395	of	of	IN
396	405	accessory	accessory	JJ
406	411	genes	gene	NNS
412	416	such	such	JJ
417	419	as	as	IN
420	423	nef	nef	NN
423	424	)	)	)
425	428	has	have	VBZ
429	433	been	be	VBN
434	443	forwarded	forward	VBN
444	446	as	as	IN
447	448	a	a	DT
449	456	primary	primary	JJ
457	465	approach	approach	NN
466	469	for	for	IN
470	478	creating	create	VBG
479	488	enfeebled	enfeeble	VBN
488	489	,	,	,
490	493	but	but	CC
494	515	replication-competent	replication-competent	JJ
515	516	,	,	,
517	526	HIV-1/SIV	HIV-1/SIV	NNP
526	527	.	.	.

528	539	Regrettably	regrettably	RB
539	540	,	,	,
541	547	recent	recent	JJ
548	556	evidence	evidence	NN
557	565	suggests	suggest	VBZ
566	570	that	that	IN
571	587	loss-of-function	loss-of-function	NN
588	593	alone	alone	RB
594	596	is	be	VBZ
597	600	not	not	RB
601	607	always	always	RB
608	618	sufficient	sufficient	JJ
619	621	to	to	TO
622	629	prevent	prevent	VB
630	633	the	the	DT
634	643	emergence	emergence	NN
644	646	of	of	IN
647	655	virulent	virulent	JJ
656	663	mutants	mutant	NNS
663	664	.	.	.

665	668	New	new	JJ
669	679	strategies	strategy	NNS
680	684	that	that	WDT
685	694	attenuate	attenuate	VBP
695	698	via	via	IN
699	709	mechanisms	mechanism	NNS
710	718	distinct	distinct	JJ
719	723	from	from	IN
724	740	loss-of-function	loss-of-function	NN
741	744	are	be	VBP
745	751	needed	need	VBN
752	755	for	for	IN
756	765	enhancing	enhance	VBG
766	769	the	the	DT
770	776	safety	safety	NN
777	786	phenotype	phenotype	NN
787	789	of	of	IN
790	795	viral	viral	JJ
796	802	genome	genome	NN
802	803	.	.	.

804	808	Here	here	RB
808	809	,	,	,
810	812	we	we	PRP
813	820	propose	propose	VBP
821	837	gain-of-function	gain-of-function	NN
838	840	to	to	TO
841	843	be	be	VB
844	848	used	use	VBN
849	863	simultaneously	simultaneously	RB
864	868	with	with	IN
869	885	loss-of-function	loss-of-function	NN
886	888	as	as	IN
889	890	a	a	DT
891	896	novel	novel	JJ
897	905	approach	approach	NN
906	909	for	for	IN
910	921	attenuating	attenuate	VBG
922	927	HIV-1	HIV-1	NNP
927	928	.	.	.

929	931	We	we	PRP
932	936	have	have	VBP
937	948	constructed	construct	VBN
949	951	an	an	DT
952	957	HIV-1	HIV-1	NNP
958	964	genome	genome	NN
965	973	carrying	carry	VBG
974	977	the	the	DT
978	982	cDNA	cdna	NN
983	985	of	of	IN
986	987	a	a	DT
988	1009	proteolysis-resistant	proteolysis-resistant	JJ
1010	1017	nuclear	nuclear	JJ
1018	1031	factor-kappaB	factor-kappab	NN
1032	1041	inhibitor	inhibitor	NN
1042	1043	(	(	(
1043	1063	IkappaB-alphaS32/36A	IkappaB-alphaS32/36A	NNP
1063	1064	)	)	)
1065	1067	in	in	IN
1068	1071	the	the	DT
1072	1075	nef	nef	NN
1076	1082	region	region	NN
1082	1083	.	.	.

1084	1089	HIV-1	HIV-1	NNP
1090	1100	expressing	express	VBG
1101	1121	IkappaB-alphaS32/36A	IkappaB-alphaS32/36A	NNP
1122	1136	down-regulates	down-regulate	VBZ
1137	1142	viral	viral	JJ
1143	1153	expression	expression	NN
1154	1157	and	and	CC
1158	1160	is	be	VBZ
1161	1167	highly	highly	RB
1168	1178	attenuated	attenuate	VBN
1179	1181	in	in	IN
1182	1186	both	both	CC
1187	1193	Jurkat	Jurkat	NNP
1194	1197	and	and	CC
1198	1208	peripheral	peripheral	JJ
1209	1214	blood	blood	NN
1215	1226	mononuclear	mononuclear	JJ
1227	1232	cells	cell	NNS
1232	1233	.	.	.

1234	1236	We	we	PRP
1237	1244	provide	provide	VBP
1245	1251	formal	formal	JJ
1252	1257	proof	proof	NN
1258	1262	that	that	IN
1263	1266	the	the	DT
1267	1277	phenotypic	phenotypic	JJ
1278	1281	and	and	CC
1282	1293	attenuating	attenuate	VBG
1294	1309	characteristics	characteristic	NNS
1310	1312	of	of	IN
1313	1333	IkappaB-alphaS32/36A	IkappaB-alphaS32/36A	NNP
1334	1340	permit	permit	VBP
1341	1344	its	its	PRP$
1345	1351	stable	stable	JJ
1352	1363	maintenance	maintenance	NN
1364	1366	in	in	IN
1367	1368	a	a	DT
1369	1373	live	live	NN
1373	1374	,	,	,
1375	1386	replicating	replicate	VBG
1387	1392	HIV-1	HIV-1	NNP
1393	1400	despite	despite	IN
1401	1404	180	180	CD
1405	1409	days	day	NNS
1410	1412	of	of	IN
1413	1419	forced	force	VBN
1420	1422	ex	ex	FW
1423	1427	vivo	vivo	FW
1428	1437	passaging	passaging	NN
1438	1440	in	in	IN
1441	1447	tissue	tissue	NN
1448	1455	culture	culture	NN
1455	1456	.	.	.

1457	1459	As	as	IN
1460	1468	compared	compare	VBN
1469	1473	with	with	IN
1474	1479	other	other	JJ
1480	1492	open-reading	open-reading	JJ
1493	1499	frames	frame	NNS
1500	1508	embedded	embed	VBN
1509	1513	into	into	IN
1514	1521	HIV/SIV	HIV/SIV	NNP
1522	1528	genome	genome	NN
1528	1529	,	,	,
1530	1534	this	this	DT
1535	1541	degree	degree	NN
1542	1544	of	of	IN
1545	1554	stability	stability	NN
1555	1557	is	be	VBZ
1558	1571	unprecedented	unprecedented	JJ
1571	1572	.	.	.

1573	1577	Thus	thus	RB
1577	1578	,	,	,
1579	1599	IkappaB-alphaS32/36A	IkappaB-alphaS32/36A	NNP
1600	1606	offers	offer	VBZ
1607	1625	proof-of-principle	proof-of-principle	JJ
1626	1630	that	that	IN
1631	1644	artifactually	artifactually	RB
1645	1651	gained	gain	VBN
1652	1661	functions	function	NNS
1661	1662	,	,	,
1663	1667	when	when	WRB
1668	1672	used	use	VBN
1673	1675	to	to	TO
1676	1685	attenuate	attenuate	VB
1686	1689	the	the	DT
1690	1701	replication	replication	NN
1702	1704	of	of	IN
1705	1709	live	live	JJ
1710	1715	HIV-1	HIV-1	NNP
1715	1716	,	,	,
1717	1720	can	can	MD
1721	1723	be	be	VB
1724	1730	stable	stable	JJ
1730	1731	.	.	.

1732	1737	These	these	DT
1738	1746	findings	finding	NNS
1747	1757	illustrate	illustrate	VBP
1758	1774	gain-of-function	gain-of-function	NN
1775	1777	as	as	IN
1778	1779	a	a	DT
1780	1788	feasible	feasible	JJ
1789	1797	strategy	strategy	NN
1798	1801	for	for	IN
1802	1812	developing	develop	VBG
1813	1818	safer	safe	JJR
1819	1834	live-attenuated	live-attenuated	JJ
1835	1839	HIVs	hiv	NNS
1840	1842	to	to	TO
1843	1845	be	be	VB
1846	1852	tested	test	VBN
1853	1855	as	as	IN
1856	1866	candidates	candidate	NNS
1867	1870	for	for	IN
1871	1875	AIDS	AIDS	NNP
1876	1883	vaccine	vaccine	NN
1883	1884	.	.	.