Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection
Abstract
Dendritic cells can capture and transfer retroviruses in vitro across synaptic cell-cell contacts to uninfected cells, a process called trans-infection. Whether trans-infection contributes to retroviral spread in vivo remains unknown. Here, we visualize how retroviruses disseminate in secondary lymphoid tissues of living mice. We demonstrate that murine leukemia virus (MLV) and human immunodeficiency virus (HIV) are first captured by sinus-lining macrophages. CD169/Siglec-1, an I-type lectin that recognizes gangliosides, captures the virus. MLV-laden macrophages then form long-lived synaptic contacts to trans-infect B-1 cells. Infected B-1 cells subsequently migrate into the lymph node to spread the infection through virological synapses. Robust infection in lymph nodes and spleen requires CD169, suggesting that a combination of fluid-based movement followed by CD169-dependent trans-infection can contribute to viral spread.
Additional Information
© 2015 American Association for the Advancement of Science. Received for publication 2 April 2015. Accepted for publication 17 September 2015. Published Online October 1 2015. We thank J. Grover, J. Ventura, K. Haugh for critical reading of the manuscript, P. Van Ness for advice with statistical analyses and P. Crocker, D. Gonzalez and A. Haberman for Siglec−/− mice and DsRed mice, respectively. Siglec−/− mice are available under a material transfer agreement with P. Crocker (University of Dundee, UK). This work was supported by the NIH grants R01 CA098727, S10 RR026697, P50GM082545 to P.J.B and W.M., R01 AI097052, R01 DA036298, P01 AI078897 to T.R.M., R01 AI112443 to P.K., Flow Cytometry Shared Resource of the Yale Cancer Center P30 CA016359, the Leopoldina Fellowship LPDS2009-21 to X.S., and a fellowship from the China Scholarship Council-Yale World Scholars to R.P. D.L. Greiner and M.A. Brehm are consultants for and receive grants from The Jackson Laboratory.Attached Files
Accepted Version - nihms-735117.pdf
Supplemental Material - Sewald.SM.pdf
Supplemental Material - aab2749s1.mov
Supplemental Material - aab2749s10.mov
Supplemental Material - aab2749s11.mov
Supplemental Material - aab2749s12.mov
Supplemental Material - aab2749s13.mov
Supplemental Material - aab2749s14.mov
Supplemental Material - aab2749s2.mov
Supplemental Material - aab2749s3.mov
Supplemental Material - aab2749s4.mov
Supplemental Material - aab2749s5.mov
Supplemental Material - aab2749s6.mov
Supplemental Material - aab2749s7.mov
Supplemental Material - aab2749s8.mov
Supplemental Material - aab2749s9.mov
Files
Name | Size | Download all |
---|---|---|
md5:478d3fe797be57e35c9c6b73e1ef4fa8
|
1.9 MB | Preview Download |
md5:83ed2e53c79f88a8e6311fe84af04b5d
|
23.7 MB | Download |
md5:fdb5b1ead227c3d16326b767728ba6e1
|
25.0 MB | Download |
md5:2e512b877b9fcf3a4ab7be4700d6a059
|
1.9 MB | Download |
md5:8e805e30295fe8dd06dd03622bf9bfc8
|
3.4 MB | Download |
md5:8d6a71f34d6a1e02c83b37bc65f0735f
|
1.1 MB | Download |
md5:bac186674e89824717a63c5ce8de19e4
|
12.7 MB | Preview Download |
md5:323f5e421fdc8ebc7a67f2a65a6c1037
|
3.7 MB | Download |
md5:99ffa62f3fca18f4dbc81ca7b8394bcf
|
2.9 MB | Download |
md5:3a20e5237130aabfd19403a3d12d90e5
|
2.6 MB | Download |
md5:2097595e938feee92243653b7b2963df
|
3.5 MB | Download |
md5:73c407e559e3f0e17d340e2331c5a5fe
|
1.8 MB | Download |
md5:791019911284c347ed7253291a3075d9
|
16.5 MB | Download |
md5:d92add805df796221d15813b0e2bb61d
|
1.3 MB | Download |
md5:a2fbe088d4da9928994c01b44c0ad2f5
|
4.5 MB | Download |
md5:4722d4f8fed8a00232892c459c74d033
|
2.4 MB | Download |
Additional details
- PMCID
- PMC4651917
- Eprint ID
- 60980
- DOI
- 10.1126/science.aab2749
- Resolver ID
- CaltechAUTHORS:20151012-130234277
- NIH
- R01 CA098727
- NIH
- S10 RR026697
- NIH
- P50GM082545
- NIH
- R01 AI097052
- NIH
- R01 DA036298
- NIH
- P01 AI078897
- NIH
- R01 AI112443
- NIH
- P30 CA016359
- Leopoldina Fellowship
- LPDS2009-21
- China Scholarship Council-Yale World Scholars
- Jackson Laboratory
- Created
-
2015-10-13Created from EPrint's datestamp field
- Updated
-
2022-05-19Created from EPrint's last_modified field