Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26529416
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26529416
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+Pathog
2015 ; 11
(11
): e1005254
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Interferon-? Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression,
Potency and Effector Mechanisms
#MMPMID26529416
Harper MS
; Guo K
; Gibbert K
; Lee EJ
; Dillon SM
; Barrett BS
; McCarter MD
; Hasenkrug KJ
; Dittmer U
; Wilson CC
; Santiago ML
PLoS Pathog
2015[]; 11
(11
): e1005254
PMID26529416
show ga
HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within
the intestinal mucosa during acute infection. The type I interferons (IFNs)
likely serve as a first line of defense, but the relative expression and
antiviral properties of the 12 IFN? subtypes against HIV-1 infection of mucosal
tissues remain unknown. Here, we evaluated the expression of all IFN? subtypes in
HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then
determined the relative antiviral potency of each IFN? subtype ex vivo using the
human intestinal Lamina Propria Aggregate Culture model. IFN? subtype transcripts
from the centromeric half of the IFNA gene complex were highly expressed in pDCs
following HIV-1 exposure. There was an inverse relationship between IFNA subtype
expression and potency. IFN?8, IFN?6 and IFN?14 were the most potent in
restricting HIV-1 infection. IFN?2, the clinically-approved subtype, and IFN?1
were both highly expressed but exhibited relatively weak antiviral activity. The
relative potencies correlated with binding affinity to the type I IFN receptor
and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but
not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional
induction, the higher relative potency of IFN?8 and IFN?14 correlated with
stronger inhibition of virion infectivity, which is linked to
deaminase-independent APOBEC3 restriction activity. By contrast, both potent
(IFN?8) and weak (IFN?1) subtypes significantly induced HIV-1 GG-to-AG
hypermutation. The results unravel non-redundant functions of the IFN? subtypes
against HIV-1 infection, with strong implications for HIV-1 mucosal immunity,
viral evolution and IFN?-based functional cure strategies.
free
free
free
