dc.contributor.author |
Barbian, HJ |
|
dc.contributor.author |
Berg, A |
|
dc.contributor.author |
Bhardwaj, N |
|
dc.contributor.author |
Bjorkman, PJ |
|
dc.contributor.author |
Borrow, P |
|
dc.contributor.author |
Cai, Fangping |
|
dc.contributor.author |
Decker, JM |
|
dc.contributor.author |
Denny, Thomas Norton |
|
dc.contributor.author |
Ding, Haitao |
|
dc.contributor.author |
Doms, RW |
|
dc.contributor.author |
Galimidi, RP |
|
dc.contributor.author |
Gao, Feng |
|
dc.contributor.author |
Giorgi, EE |
|
dc.contributor.author |
Hahn, Beatrice H |
|
dc.contributor.author |
Haynes, Barton Ford |
|
dc.contributor.author |
Hopper, J |
|
dc.contributor.author |
Hora, Bhavna |
|
dc.contributor.author |
Iyer, SS |
|
dc.contributor.author |
Kappes, JC |
|
dc.contributor.author |
Korber, Bette T |
|
dc.contributor.author |
Li, H |
|
dc.contributor.author |
Muldoon, M |
|
dc.contributor.author |
O'Brien, M |
|
dc.contributor.author |
Ochsenbauer, C |
|
dc.contributor.author |
Parrish, EH |
|
dc.contributor.author |
Parrish, NF |
|
dc.contributor.author |
Shaw, GM |
|
dc.contributor.author |
Theiler, JP |
|
dc.contributor.author |
West, AP |
|
dc.contributor.author |
Wilen, CB |
|
dc.contributor.author |
Zajic, L |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2017-06-01T20:32:52Z |
|
dc.date.available |
2017-06-01T20:32:52Z |
|
dc.date.issued |
2013-04-23 |
|
dc.identifier |
https://www.ncbi.nlm.nih.gov/pubmed/23542380 |
|
dc.identifier |
1304288110 |
|
dc.identifier.uri |
https://hdl.handle.net/10161/14727 |
|
dc.description.abstract |
Defining the virus-host interactions responsible for HIV-1 transmission, including
the phenotypic requirements of viruses capable of establishing de novo infections,
could be important for AIDS vaccine development. Previous analyses have failed to
identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell
tropism that are preferentially associated with viral transmission. However, most
of these studies were limited to examining envelope (Env) function in the context
of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder
(TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C
(n = 23) and compared their phenotypic properties in assays specifically designed
to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold
more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048)
compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic
cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T
cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable
kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated
to higher titers than CC viruses. This difference was significant for subtype B (P
= 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic
differences of the respective patient cohorts. Together, these data indicate that
TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved
dendritic cell interaction, and relative IFN-α resistance. These viral properties,
which likely act in concert, should be considered in the development and testing of
AIDS vaccines.
|
|
dc.language |
eng |
|
dc.relation.ispartof |
Proc Natl Acad Sci U S A |
|
dc.relation.isversionof |
10.1073/pnas.1304288110 |
|
dc.subject |
Base Sequence |
|
dc.subject |
CD4-Positive T-Lymphocytes |
|
dc.subject |
Cloning, Molecular |
|
dc.subject |
Dendritic Cells |
|
dc.subject |
Enzyme-Linked Immunosorbent Assay |
|
dc.subject |
HIV Infections |
|
dc.subject |
HIV-1 |
|
dc.subject |
Humans |
|
dc.subject |
Linear Models |
|
dc.subject |
Molecular Sequence Data |
|
dc.subject |
Phenotype |
|
dc.subject |
Sequence Analysis, DNA |
|
dc.subject |
Viral Envelope Proteins |
|
dc.subject |
Virion |
|
dc.title |
Phenotypic properties of transmitted founder HIV-1. |
|
dc.type |
Journal article |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/23542380 |
|
pubs.begin-page |
6626 |
|
pubs.end-page |
6633 |
|
pubs.issue |
17 |
|
pubs.organisational-group |
Basic Science Departments |
|
pubs.organisational-group |
Clinical Science Departments |
|
pubs.organisational-group |
Duke |
|
pubs.organisational-group |
Duke Cancer Institute |
|
pubs.organisational-group |
Duke Human Vaccine Institute |
|
pubs.organisational-group |
Immunology |
|
pubs.organisational-group |
Institutes and Centers |
|
pubs.organisational-group |
Medicine |
|
pubs.organisational-group |
Medicine, Duke Human Vaccine Institute |
|
pubs.organisational-group |
Medicine, Infectious Diseases |
|
pubs.organisational-group |
School of Medicine |
|
pubs.publication-status |
Published |
|
pubs.volume |
110 |
|
dc.identifier.eissn |
1091-6490 |
|