Rational CCL5 mutagenesis integration in a lactobacilli platform generates extremely potent HIV-1 blockers.
Rational CCL5 mutagenesis integration in a lactobacilli platform generates extremely potent HIV-1 blockers.
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DOI：
10.1038/s41598-018-20300-9
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发表时间：
2018-01-30
影响因子：
4.6
通讯作者：
Vangelista L
中科院分区：
文献类型：
--
作者：
Secchi M;Grampa V;Vangelista L
Efforts to improve existing anti-HIV-1 therapies or develop preventatives have identified CCR5 as an important target and CCL5 as an ideal scaffold to sculpt potent HIV-1 entry inhibitors. We created novel human CCL5 variants that exhibit exceptional anti-HIV-1 features using recombinant lactobacilli (exploited for live microbicide development) as a screening platform. Protein design, expression and anti-HIV-1 activity flowed in iterative cycles, with a stepwise integration of successful mutations and refinement of an initial CCL5 mutant battery towards the generation of two ultimate CCL5 derivatives, a CCR5 agonist and a CCR5 antagonist with similar anti-HIV-1 potency. The CCR5 antagonist was tested in human macrophages and against primary R5 HIV-1 strains, exhibiting cross-clade low picomolar IC50 activity. Moreover, its successful combination with several HIV-1 inhibitors provided the ground for conceiving therapeutic and preventative anti-HIV-1 cocktails. Beyond HIV-1 infection, these CCL5 derivatives may now be tested against several inflammation-related pathologies where the CCL5:CCR5 axis plays a relevant role.
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影响因子：
56.9
作者：
COCCHI, F;DEVICO, AL;LUSSO, P
通讯作者：
LUSSO, P
影响因子：
4.8
作者：
Czaplewski, LG;McKeating, J;Hunter, MG
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Hunter, MG
影响因子：
16.8
作者：
Appay, V;Rowland-Jones, SL
通讯作者：
Rowland-Jones, SL
影响因子：
3.4
作者：
Klasse PJ
通讯作者：
Klasse PJ
DOI：
10.1073/pnas.0805098105
发表时间：
2008-11-18
影响因子：
11.1
作者：
Gaertner, Hubert;Cerini, Fabrice;Hartley, Oliver
通讯作者：
Hartley, Oliver