Table 1.
Overview of experimental HIV-1 Tat functional variants
| Tat Residue Variant | Length | Subtype | Functional Alteration(s) | Reference | Year |
|---|---|---|---|---|---|
| Q2A | 86 | B | Trp11 exposure at neutral pH | Yezid, et al | 2009 |
| W11A | 86 | B | Decrease in LTR transactivation | Yezid, et al | 2009 |
| W11L | Decrease in LTR transactivation | Yezid, et al | 2009 | ||
| W11Y | Decrease in LTR transactivation | Yezid, et al | 2009 | ||
| Unable to be secreted | Rayne, et al | 2010 | |||
| W11F | Decrease in LTR transactivation | Yezid, et al | 2009 | ||
| Unable to be secreted | Rayne, et al | 2010 | |||
| H13L | 72 | B | Decreased LTR transactivation; unable to bind p-TEFb | Reza, et al | 2003 |
| S16A | 86 | B | Reduction in posttranslational | Ammosova, et al | 2006 |
| phosphorylation; decrease in LTR transactivation; reduction in viral replication | |||||
| 86 | Not specified | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Tyagi, et al | 2011 | |
| 101 | Not specified | Resistant to phosphorylation by CDK2; decrease in LTR transactivation | Ivanov, et al | 2018 | |
| S16D | 101 | Not specified | Resistant to phosphorylation by CDK2; decrease in LTR transactivation | Ivanov, et al | 2018 |
| S16,46A | 86 | B | Reduction in posttranslational phosphorylation; decrease in LTR transactivation; reduction in viral replication | Ammosova, et al | 2006 |
| C22A | Not specified | Not specified | Ablation of binding to P-TEFb | D’Orso, et al | 2012 |
| 86 | B | Unable to bind PJA2 E3 ubiquitin ligase | Faust, et al | 2017 | |
| C22G | 72 | B | Decrease in LTR transactivation | Reza, et al | 2003 |
| 72, 101 | Not specified | Resistant to ubiquitination by Hdm2 | Bres, et al | 2003 | |
| 86 | B | Reduction in binding efficiency to NF-κB | Dandekar, et al | 2004 | |
| 86 | B | Reduction in neurotoxicity; inability to activate caspase-9, caspase-3, and caspase-7 | Aksenov, et al | 2009 | |
| 86 | B | Restored normal levels of | Aksenov, et | 2010 | |
| amyloid beta production; rescued cell viability | al | ||||
| 101 | Not specified | Reduction of hyperacetylation of the p65 subunit of NF-κB | Kwon, et al | 2008 | |
| 86 | B | Protection from reduction of F-actin puncta; protection from reduction in total dendrite branch number | Bertrand, et al | 2013 | |
| 86 | B | Decrease in LTR transactivation | Rice and Carlotti | 1990 | |
| 86 | B | Decrease in TAR-independent LTR transactivation | Yang, et al | 1997 | |
| Not specified | B | Unable to bind LTR promotor domains | Southgate and Green | 1991 | |
| Not specified | Not specified | Increased apoptosis of Jurkat T cells; decreased Bcl-2 levels | Zauli, et al | 1995 | |
| C22S | 72 | C | Decrease in LTR transactivation | Huet, et al | 1989 |
| 72 | B | Decrease in LTR transactivation | Garcia, et al | 1988 | |
| 86 | B | Reduced synaptodendritic injury | Bertrand, et al | 2013 | |
| C22,25,2 7A | 86 | Not specified | Reduction in HUVEC proliferation and migration; reduction in VEGFR-2 phosphorylation | Mitola, et al | 2000 |
| T23D | 86 | Not specified | Decrease in LTR transactivation | Yoon, et al | 2015 |
| Y26A | 86 | B | Decrease in LTR transactivation; reduction in viral replication | Verhoef, et al | 1997 |
| 72 | B | Decrease in TAR- | Das, et al | 2011 | |
| independent LTR transactivation | |||||
| C27S | 72 | B | Decrease in LTR transactivation | Garcia, et al | 1988 |
| K28Q | 72 | B | Decrease in nuclear import; decrease in LTR transactivation; delayed replication kinetics; reduction in binding efficiency to CycT1; atypical subcellular localization | Bres, et al | 2002 |
| Not specified | Not specified | Decrease in LTR transactivation | D’Orso and Frankel | 2009 | |
| K28R | 72 | B | Decrease in nuclear import; decrease in LTR transactivation; reduction in binding efficiency to CycT1; atypical subcellular localization; reduction in binding efficiency to PCAF | Bres, et al | 2002 |
| 86 | B | Decrease in LTR transactivation | Faust, et al | 2017 | |
| Not specified | Not specified | Reduction in acetylation by PCAF; delayed viral replication kinetics | D’Orso and Frankel | 2009 | |
| C30G | 86 | B | Decrease in LTR transactivation | Rice and Carlotti | 1990 |
| C30S | 72 | C | Reduction in primary PBMC migration; decrease in LTR transactivation | Ranga, et al | 2004 |
| C31G | 86 | B | Decrease in LTR transactivation | Rice and Carlotti | 1990 |
| 72 | B | Decrease in LTR transactivation | Reza, et al | 2003 | |
| C31S | 72 | C | Reduction in primary | Ranga, et al | 2004 |
| PBMC migration | |||||
| 72 | C | Protection from Tat-mediated neurotoxicity | Li, et al | 2008 | |
| 101 | C | Restored normal levels of amyloid beta production; restored cell viability | Aksenov, et al | 2010 | |
| 101 | C | Reduced synaptodendritic injury | Bertrand, et al | 2013 | |
| C31H | Not specified | B | Decrease in LTR transactivation | Sadaie, et al | 1990 |
| W32G | 101 | E | Restoration of P/CAF and GCN5 HAT chromatin remodeling; restored expression of TNF genes | Ranjbar, et al | 2006 |
| H33A | Not specified | B | Decrease in TAR-independent LTR transactivation | Southgate and Green | 1991 |
| 86 | B | Decrease in LTR transactivation | Rice and Carlotti | 1990 | |
| C34H | Not specified | B | Decrease in LTR transactivation | Sadaie, et al | 1990 |
| C34,37H | Not specified | B | Decrease in LTR transactivation | Sadaie, et al | 1990 |
| C34S | 72 | B | Decrease in LTR transactivation | Garcia, et al | 1988 |
| C34G | 67 | B | Decrease in LTR transactivation | Kuppuswam y, et al | 1989 |
| Not specified | B | Decreased protein stability | Sadaie, et al | 1990 | |
| Q35A | 86 | B | Decrease in TAR-independent LTR transactivation | Yang, et al | 1997 |
| 36,37,38, 39A | Not specified | B | Reduction in binding efficiency to tubulin; unable to activate | Chen, et al | 2002 |
| caspase-9 | |||||
| C37H | Not specified | B | Decrease in LTR transactivation | Sadaie, et al | 1990 |
| C37G | 67 | B | Decrease in LTR transactivation | Kuppuswam y, et al | 1989 |
| F38A | 101 | Not specified | Reduction of hyperacetylation of the p65 subunit of NF-κB | Kwon, et al | 2008 |
| Not specified | B | Decrease in TAR-independent LTR transactivation | Southgate and Green | 1991 | |
| 86 | B | Decrease in LTR transactivation | Rice and Carlotti | 1990 | |
| T40D | 86 | Not specified | Decrease in LTR transactivation | Yoon, et al | 2015 |
| K41A | 101 | Not specified | Reduction of hyperacetylation of the p65 subunit of NF-κB; increase the expression of IL-2 | Kwon, et al | 2008 |
| 72 | B | Decrease in nuclear import; decrease in LTR transactivation; reduction in binding to CycT1; reduction in binding efficiency to PCAF | Bres, et al | 2002 | |
| Not specified | Not specified | Decrease in efficiency of p-TEFb binding | D’Orso, et al | 2012 | |
| Not specified | B | Decrease in TAR-independent LTR transactivation | Southgate and Green | 1991 | |
| 86 | B | Decrease in LTR transactivation | Rice and Carlotti | 1990 | |
| K41Q | 101 | Not specified | Increase in nuclear localization | He, et al | 2013 |
| K41R | 86 | B | Reduction in binding efficiency to BRG1; decrease in LTR transactivation | Agbottah, et al | 2006 |
| 86 | B | Decrease in LTR transactivation; resistant to ubiquitination by PJA2 | Faust, et al | 2017 | |
| 101 | Not specified | Decreased nuclear localization | He, et al | 2013 | |
| K41T | 101 | Not specified | Decrease in LTR transactivation | El Kharroubi, et al | 1998 |
| S46A | 86 | B | Reduction in posttranslational phosphorylation; decrease in LTR transactivation; reduction in viral replication | Ammosova, et al | 2006 |
| 101 | Not specified | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Ivanov, et al | 2018 | |
| S46D | 86 | Not specified | Decrease in LTR transactivation | Yoon, et al | 2015 |
| 101 | Not specified | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Ivanov, et al | 2018 | |
| Y47A | 101 | Not specified | Reduction in binding efficiency to PCAF; decrease in LTR transactivation | Dorr, et al | 2002 |
| R49,53A | 72 | B | Decrease in LTR transactivation | Xie, et al | 2007 |
| R49G,K50I | 86 | Not specified | Reduction in HUVEC proliferation and migration; reduction in | Mitola, et al | 2000 |
| VEGFR-2 phosphorylation | |||||
| R49G,K5 0I,R52L, R53I | 86 | Not specified | Reduction in HUVEC proliferation and migration; reduction in VEGFR-2 phosphorylation | Mitola, et al | 2000 |
| K50A | 101 | Not specified | Increase in expression of CRLF2, BDNF, APBA1; decrease in expression of C5 | Carvallo, et al | 2017 |
| 101 | Not specified | Decrease in LTR transactivation | Ott, et al | 1999 | |
| 86 | Not specified | Resistant to methylation by SETDB1 | Van Duyne, et al | 2008 | |
| K50R | 101 | Not specified | Decrease in LTR transactivation | Dorr, et al | 2002 |
| 72 | B | Increase in nuclear localization; reduction in viral replication | Bres, et al | 2002 | |
| 101 | Not specified | Decrease in LTR transactivation; reduction in binding efficiency to CycT1; resistant to acetylation by p300/CBP | Ott, et al | 1999 | |
| 86 | B | Reduction in binding efficiency to BRG1; decrease in LTR transactivation | Agbottah, et al | 2006 | |
| K50Q | 72 | B | Decrease in nuclear import; decrease in LTR transactivation | Bres, et al | 2002 |
| K50,51A | 86 | Not specified | Resistant to methylation by SETDB1 | Van Duyne, et al | 2008 |
| K50,51R | 101 | Not | Decrease in LTR | Ott, et al | 1999 |
| specified | transactivation | ||||
| K50S,K5 1G | 101 | B | Reduced RNA binding efficiency | Bouwman, et al | 2014 |
| K51A | 86 | Not specified | Resistant to methylation by SETDB1 | Van Duyne, et al | 2008 |
| K51R | 72 | Not specified | Decrease in LTR transactivation | Ali, et al | 2016 |
| 86 | B | Reduction in binding efficiency to BRG1; decrease in LTR transactivation | Agbottah, et al | 2006 | |
| 101 | Not specified | Decrease in LTR transactivation | Dorr, et al | 2002 | |
| K51,71R | 72 | Not specified | Decrease in LTR transactivation | Ali, et al | 2016 |
| 52GGQGGG57 | 72 | Not specified | Inhibition of association with nucleophosmin; decreased nuclear localization | Li, et al | 1997 |
| R52K | 72 | B | Decrease in LTR transactivation | Xie, et al | 2007 |
| 101 | Not specified | Resistant to methylation by PRMT6 | Fulcher, et al | 2016 | |
| R52,53K | 72 | B | Decrease in LTR transactivation | Xie, et al | 2007 |
| R53A | 101 | Not specified | Reduction in binding efficiency to PCAF; decrease in LTR transactivation | Dorr, et al | 2002 |
| R53K | 101 | Not specified | Resistant to methylation by PRMT7 | Fulcher, et al | 2016 |
| R53E | 101 | Not | Reduction in binding | Dorr, et al | 2002 |
| specified | efficiency to PCAF | ||||
| 55AAA57 | 86 | B | Trp11 exposure at neutral pH | Yezid, et al | 2009 |
| S62A | 86 | B | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Endo-Munoz, et al | 2005 |
| 86 | Not specified | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Tyagi, et al | 2011 | |
| S62D | 86 | Not specified | Decrease in LTR transactivation | Yoon, et al | 2015 |
| S62,64,68 A | 86 | B | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Endo-Munoz, et al | 2005 |
| T64A | 86 | B | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Endo-Munoz, et al | 2005 |
| S68A | 86 | B | Resistant to phosphorylation by PKR; decrease in LTR transactivation | Endo-Munoz, et al | 2005 |
| S68D | 86 | Not specified | Decrease in LTR transactivation | Yoon, et al | 2015 |
| K71A | 72 | Not specified | Resistant to methylation by KMT7 | Ali, et al | 2016 |
| K71R | 72 | Not specified | Decrease in LTR transactivation; resistant to methylation by KMT7 | Ali, et al | 2016 |
| 72, 101 | Not specified | Decrease in LTR transactivation, resistant to ubiquitination by | Bres, et al | 2003 | |
| Hdm2 | |||||
| Q78R | Not specified | C | Increased apoptosis of THP-1 cells | Sood, et al | 2008 |
| R78K/D8 0E | 86 | B | Reduced HUVEC proliferation, migration, and adhesion to extracellular matrix | Mitola, et al | 2000 |
| K88R | 101 | Not specified | Decrease in nuclear localization | He, et al | 2013 |
| K89R | 101 | Not specified | Increase in nuclear localization | He, et al | 2013 |
| K88,89,9 0A | 101 | B | Decrease in TAR-independent LTR transactivation | Mahlknecht, et al | 2008 |
| K90R | 101 | Not specified | Decrease in nuclear localization | He, et al | 2013 |
| E92,94,9 6A | 101 | B | Decrease in TAR-independent LTR transactivation | Mahlknecht, et al | 2008 |