• Something wrong with this record ?

HIV-1 envelope glycan moieties modulate HIV-1 transmission

R. Shen, M. Raska, D. Bimczok, J. Novak, PD. Smith,

. 2014 ; 88 (24) : 14258-67.

Language English Country United States

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.

E-resources Online Full text

NLK Free Medical Journals from 1967 to 6 months ago
Freely Accessible Science Journals from 1967 to 6 months ago
PubMed Central from 1967 to 1 year ago
Europe PubMed Central from 1967 to 6 months ago
Open Access Digital Library from 1967-02-01
Open Access Digital Library from 1967-02-01

UNLABELLED: The HIV-1 envelope protein (Env) is heavily glycosylated, with approximately 50% of the Env molecular mass being contributed by N-glycans. HIV-1 Env N-glycans shield the protein backbone and have been shown to play key roles in determining Env structure, surface exposure, and, consequently, antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. Also, the role of Env glycan moieties on HIV-1 transmission has not been systematically defined. Using viruses with modified Env glycan content and heterogeneity, we examined the effects of Env glycan moieties on the major events of HIV-1 transmission. Compared to viruses with less oligomannose and more complex Env glycans, viruses with more oligomannose and less complex glycans more efficiently (i) transcytosed across an epithelial cell monolayer, (ii) attached to monocyte-derived macrophages (MDMs), (iii) bound monocyte-derived dendritic cells (MoDCs), and (iv) trans-infected primary lymphocytes via MoDCs. However, viruses with more oligomannose and less complex glycans displayed impaired infectivity in TZMbl cells, MDMs, primary lymphocytes, and fresh human intestinal tissue. Thus, N-linked Env glycans display discordant effects on the major events of HIV-1 transmission, with mature oligosaccharide structures on Env playing a crucial role in HIV-1 infection. Env glycosylation should be taken into consideration in the development of vaccine strategies to interdict HIV-1 transmission. IMPORTANCE: HIV-1 Env N-glycans shield the protein backbone and play key roles in determining Env structure and surface exposure, thereby impacting Env antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. In the study described in this report, we investigated systematically the role of Env glycan moieties on HIV-1 transmission. We show that N-linked Env glycans display discordant effects on the major events of HIV-1 transmission. These data indicate that Env glycan moieties impact HIV-1 transmission and that modulation of Env glycan moieties offers a potential strategy for the development of therapeutic or prophylactic vaccines against HIV-1.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15014038
003      
CZ-PrNML
005      
20150421092107.0
007      
ta
008      
150420s2014 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1128/JVI.02164-14 $2 doi
035    __
$a (PubMed)25275130
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Shen, Ruizhong $u Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA rshen@uab.edu pdsmith@uab.edu.
245    10
$a HIV-1 envelope glycan moieties modulate HIV-1 transmission / $c R. Shen, M. Raska, D. Bimczok, J. Novak, PD. Smith,
520    9_
$a UNLABELLED: The HIV-1 envelope protein (Env) is heavily glycosylated, with approximately 50% of the Env molecular mass being contributed by N-glycans. HIV-1 Env N-glycans shield the protein backbone and have been shown to play key roles in determining Env structure, surface exposure, and, consequently, antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. Also, the role of Env glycan moieties on HIV-1 transmission has not been systematically defined. Using viruses with modified Env glycan content and heterogeneity, we examined the effects of Env glycan moieties on the major events of HIV-1 transmission. Compared to viruses with less oligomannose and more complex Env glycans, viruses with more oligomannose and less complex glycans more efficiently (i) transcytosed across an epithelial cell monolayer, (ii) attached to monocyte-derived macrophages (MDMs), (iii) bound monocyte-derived dendritic cells (MoDCs), and (iv) trans-infected primary lymphocytes via MoDCs. However, viruses with more oligomannose and less complex glycans displayed impaired infectivity in TZMbl cells, MDMs, primary lymphocytes, and fresh human intestinal tissue. Thus, N-linked Env glycans display discordant effects on the major events of HIV-1 transmission, with mature oligosaccharide structures on Env playing a crucial role in HIV-1 infection. Env glycosylation should be taken into consideration in the development of vaccine strategies to interdict HIV-1 transmission. IMPORTANCE: HIV-1 Env N-glycans shield the protein backbone and play key roles in determining Env structure and surface exposure, thereby impacting Env antigenicity, infectivity, antibody neutralization, and carbohydrate and receptor binding. Studies of HIV-1 glycosylation have focused mainly on the position of glycosylation, rather than the types of glycans. In the study described in this report, we investigated systematically the role of Env glycan moieties on HIV-1 transmission. We show that N-linked Env glycans display discordant effects on the major events of HIV-1 transmission. These data indicate that Env glycan moieties impact HIV-1 transmission and that modulation of Env glycan moieties offers a potential strategy for the development of therapeutic or prophylactic vaccines against HIV-1.
650    _2
$a kultivované buňky $7 D002478
650    _2
$a dendritické buňky $x virologie $7 D003713
650    _2
$a epitelové buňky $x virologie $7 D004847
650    _2
$a HIV-1 $x fyziologie $7 D015497
650    _2
$a lidé $7 D006801
650    _2
$a lymfocyty $x virologie $7 D008214
650    _2
$a makrofágy $x virologie $7 D008264
650    _2
$a polysacharidy $x analýza $x metabolismus $7 D011134
650    12
$a přichycení viru $7 D053585
650    _2
$a genové produkty env - virus lidské imunodeficience $x chemie $x metabolismus $7 D054299
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
655    _2
$a Research Support, U.S. Gov't, Non-P.H.S. $7 D013486
700    1_
$a Raska, Milan $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA Department of Immunology, Palacky University in Olomouc, Olomouc, Czech Republic.
700    1_
$a Bimczok, Diane $u Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
700    1_
$a Novak, Jan $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
700    1_
$a Smith, Phillip D $u Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA VA Medical Center, Birmingham, Alabama, USA rshen@uab.edu pdsmith@uab.edu.
773    0_
$w MED00003048 $t Journal of virology $x 1098-5514 $g Roč. 88, č. 24 (2014), s. 14258-67
856    41
$u https://pubmed.ncbi.nlm.nih.gov/25275130 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20150420 $b ABA008
991    __
$a 20150421092406 $b ABA008
999    __
$a ok $b bmc $g 1071619 $s 896916
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 88 $c 24 $d 14258-67 $i 1098-5514 $m Journal of virology $n J Virol $x MED00003048
LZP    __
$a Pubmed-20150420

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...