| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-170 |
Sentence |
denotes |
Potent and stable attenuation of live-HIV-1 by gain of a proteolysis-resistant inhibitor of NF-kappaB (IkappaB-alphaS32/36A) and the implications for vaccine development. |
| T2 |
171-294 |
Sentence |
denotes |
Live-attenuated human immunodeficiency viruses (HIVs) are candidates for Acquired Immunodeficiency Syndrome (AIDS) vaccine. |
| T3 |
295-526 |
Sentence |
denotes |
Based on the simian immunodeficiency virus (SIV) model for AIDS, loss-of-function (e.g. deletion of accessory genes such as nef) has been forwarded as a primary approach for creating enfeebled, but replication-competent, HIV-1/SIV. |
| T4 |
527-663 |
Sentence |
denotes |
Regrettably, recent evidence suggests that loss-of-function alone is not always sufficient to prevent the emergence of virulent mutants. |
| T5 |
664-802 |
Sentence |
denotes |
New strategies that attenuate via mechanisms distinct from loss-of-function are needed for enhancing the safety phenotype of viral genome. |
| T6 |
803-927 |
Sentence |
denotes |
Here, we propose gain-of-function to be used simultaneously with loss-of-function as a novel approach for attenuating HIV-1. |
| T7 |
928-1082 |
Sentence |
denotes |
We have constructed an HIV-1 genome carrying the cDNA of a proteolysis-resistant nuclear factor-kappaB inhibitor (IkappaB-alphaS32/36A) in the nef region. |
| T8 |
1083-1232 |
Sentence |
denotes |
HIV-1 expressing IkappaB-alphaS32/36A down-regulates viral expression and is highly attenuated in both Jurkat and peripheral blood mononuclear cells. |
| T9 |
1233-1455 |
Sentence |
denotes |
We provide formal proof that the phenotypic and attenuating characteristics of IkappaB-alphaS32/36A permit its stable maintenance in a live, replicating HIV-1 despite 180 days of forced ex vivo passaging in tissue culture. |
| T10 |
1456-1571 |
Sentence |
denotes |
As compared with other open-reading frames embedded into HIV/SIV genome, this degree of stability is unprecedented. |
| T11 |
1572-1730 |
Sentence |
denotes |
Thus, IkappaB-alphaS32/36A offers proof-of-principle that artifactually gained functions, when used to attenuate the replication of live HIV-1, can be stable. |
| T12 |
1731-1883 |
Sentence |
denotes |
These findings illustrate gain-of-function as a feasible strategy for developing safer live-attenuated HIVs to be tested as candidates for AIDS vaccine. |