Wilen Lab


Selected Publications


Tropism for tuft cells determines immune promotion of norovirus pathogenesis.

Science. (2018)

Graphical Abstract-2 JPEG

Genome-wide CRISPR screen reveals host factors critical for SARS-CoV-2 infection

Cell. (2020)


Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes

PLoS Biology. (2021)

All Publications


*Ravindra NG, *Alfajaro MM, *Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, *van Dijk D, *Wilen CB.. Single-cell longitudinal analysis of SARS-CoV2 infection of the human airway epithelium. PLoS Biology. 2021. Pubmed


*Flynn RA, Belk JA, Qi Y, Yasumoto Y, Wei J, Alfajaro MM, Shi Q, Mumbach MR, Limaye A, DeWeirdt PC, Schmitz CO, Parker KR, Woo E, Chang HY, Horvath TL, Carette JE, Bertozzi CR, *Wilen CB, *Satpathy AT. Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021. Pubmed.


Wei J, Alfajaro MM, Hanna RE, DeWeirdt PC, Strine MS, Lu-Culligan WJ, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Gasque V, de Miguel F, Chen H, Oguntuyo K, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach B, Politi K, van Dijk D, Simon MD, Yan Q, *Doench JG, *Wilen CB. Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection. Cell. 2021. Pubmed


Ott IM, Strine MS, Watkins AE, Boot M, Kalinich CC, Harden CA, Vogels CBF, Casanovas-Massana A, Moore AJ, Muenker MC, Nakahata M, Tokuyama M, Nelson A, Fournier J, Bermejo S, Campbell M, Datta R, Dela Cruz CS, Farhadian SF, Ko AI, Iwasaki A, Grubaugh ND, Wilen CB, Wyllie AL; Yale IMPACT Research team3. Stability of SARS-CoV-2 RNA in Nonsupplemented Saliva. Emerging Infectious Diseases. 2021. Pubmed.


*Walker FC, *Hassan E, Peterson ST, Rodgers R, Schriefer LA, Thompson CE, Li Y, Kalugotla G, Blum-Johnston C, Lawrence D, McCune BT, Graziano VR, Lushniak L, Lee S, Roth AN, Karst SM, Nice TJ, Miner JJ, *Wilen CB, *Baldridge MT. Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. PLoS Pathogens. 2021. Pubmed


Huston NC, Wan H, Strine MS, de Cesaris Araujo Tavares R, Wilen CB, Pyle AM. Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms. Molecular Cell. 2021. Pubmed


Chen JS, Alfajaro MM, Chow RD, Wei J, Filler RB, Eisenbarth SC, Wilen CB. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection. Journal of Virology. 2021. Pubmed.


Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A.. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal of Experimental Medicine. 2021. Pubmed


Balce DR, Wang YT, McAllaster MR, Dunlap BF, Orvedahl A, Hykes BL Jr, Droit L, Handley SA, Wilen CB, Doench JG, Orchard RC, Stallings CL, Virgin HW. UFMylation inhibits the proinflammatory capacity of interferon-γ-activated macrophages. Proc Natl Acad Sci U S A. 2021. Pubmed.


Stites E, Wilen CB. The Interpretation of SARS-CoV-2 Diagnostic Tests. Med. 2020. Pubmed


Tada T, Fan C, Chen JS, Kaur R, Stapleford KA, Gristick H, Dcosta BM, Wilen CB, Nimigean CM, Landau NR. An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2. Cell Reports. 2020. Pubmed.


Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf conditional knockout mouse reveals strain-specific cellular tropism for murine norovirus. Journal of Virology. 2020. Pubmed.


Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL Jr, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL.Cell Metabolism. 2020. Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity. Pubmed


Ott IM, Strine MS, Watkins AE, Boot M, Kalinich CC, Harden CA, Vogels CBF, Casanovas-Massana A, Moore AJ, Muenker MC, Nakahata M, Tokuyama M, Nelson A, Fournier J, Bermejo S, Campbell M, Datta R, Dela Cruz CS, Farhadian SF, Ko AI, Iwasaki A, *Grubaugh ND, *Wilen CB, *Wyllie AL.Simply saliva: stability of SARS-CoV-2 detection negates the need for expensive collection devices. medrxiv. 2020. Pubmed


Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal of Experimental Medicine. 2020 Pubmed


Farhadian S, Glick L, Vogels C, Thomas J, Chiarella J, Cassanovas-Massana A, Zhou J, Odio C, Vijayakumar P, Geng B, Fournier J, Bermejo S, Fauver JR, Alpert T, Wyllie A, Tucotte C, Steinle M, Pczowski P, Dela Cruz C, Wilen CB, Ko AI, Mckay S, Grurbaugh ND, Spudich S, Barakat L. Seizure as a first presentation of COVID19 associated with neuroinflammation but not with viral neuroinvasion. BMC Neurology. 2020. Pubmed


Furlong K, Biering SB, Choi J, Wilen CB, Orchard RC, Wobus CE, Nelson CA, Fremont DH, Baldridge MT, Randall G, Hwang S. CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner. Journal of Virology. 2020. Pubmed


Graziano VR, Walker FC, Kennedy EA, Wei J, Ettayebi K, Strine MS, Filler RB, Hassan E, Hsieh LL, Kim AS, Kolawole AO, Wobus CE, Lindesmith LC, Baric RS, Estes MK, Orchard RC, Baldridge MT, Wilen CB. CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. PLoS Pathogens. 2020 Apr 6. Pubmed


Urbanek K, Sutherland DM, Orchard RC, Wilen CB, Knowlton JJ, Aravamudhan P, Taylor GM, Virgin HW, Dermody TS. Cytidine Monophosphate N-Acetylneuraminic Acid Synthetase and Solute Carrier Family 35 Member A1 Are Required for Reovirus Binding and Infection. Journal of Virology. 2020. Pubmed.


Wang YT, Zaitsev K, Lu Q, Li S, Schaiff WT, Kim KW, Droit L, Wilen CB, Desai C, Balce DR, Orchard RC, Orvedahl A, Park S, Kreamalmeyer D, Handley SA, Pfeifer JD, Baldridge MT, Artyomov MN, Stallings CL, Virgin HW. Select autophagy genes maintain quiescence of tissue-resident macrophages and increase susceptibility to Listeria monocytogenes. Nature Microbiology. 2020 Feb 5. Pubmed


Grau KR, Zhu S, Peterson ST, Helm EW, Philip D, Phillips M, Hernandez A, Turula H, Frasse P, Graziano VR, Wilen CB, Wobus CE, Baldridge MT, Karst SM. The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon. Nature Microbiology. 2020 Jan 5. Pubmed



Hosmillo M#, Lu J#, McAllaster MR#, Eaglesham JB,  Wang X,  Emmott E, Domingues P,  Chaudhry Y,  Fitzmaurice TJ,  Tung MKH, Panas M, McInerney G,  Locker N, Wilen CB*, Goodfellow I*. Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation. . eLife. 2019 Aug 12. Pubmed


Sherman MB, Williams AN, Smith HQ, Nelson C, Wilen CB, Fremont DH, Virgin HW, SmithTJ. Bile salts alter the mouse norovirus capsid conformation; possible implications for cell attachment and immune evasion. Journal of Virology. 2019 Epub. Pubmed


Graziano VR, Wei J, Wilen CB. Norovirus Attachment and Entry. Viruses. 2019 May 30. Pubmed


Fritzlar S, Aktepe TE, Chao YW, Kenney ND, McAllaster MR, Wilen CB, White PA, Mackenzie JM. Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis. MBio. 2019 Jun 18;10(3). Pubmed


Lee S, Liu H, Wilen CB, Sychev ZE, Desai C, Hykes BL Jr, Orchard RC, McCune BT, Kim KW, Nice TJ, Handley SA, Baldridge MT, Amarasinghe GK, Virgin HW. A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis. Cell Host & Microbe. 2019 May 21. Pubmed


Orchard RC, Wilen CB, Virgin HW. Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection. Nature Microbiology. 2018; 3(10):1109-1114. Pubmed


Nelson CA*, Wilen CB*, Dai YN, Orchard RC, Kim AS, Stegeman RA, Hsieh LL, Smith TJ, Virgin HW, Fremont DH. Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115(39):E9201-E9210. Pubmed


Liu TC, Kern JT, VanDussen KL, Xiong S, Kaiko GE, Wilen CB, Rajala MW, Caruso R, Holtzman MJ, Gao F, McGovern DP, Nunez G, Head RD, Stappenbeck TS. Interactionbetween smoking and ATG16L1T300A triggers Paneth cell defects in Crohn's disease. Journal of Clinical Investigation. 2018. Pubmed


Wilen CB, Lee S, Hsieh LY, Orchard RC, Desai C, Hykes BL, McAllaster M, Balce D, Feehley T, Brestoff JR, Hickey CA, Yokoyama CC, Wang Y, MacDuff D, Kreamalmayer D, Howitt MR, Neil JA, Cadwell K, Allen PA, Handley SA, van lookeren Campagne M, Baldridge MT, Virgin HW. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science.(2018) Apr 13. Pubmed


McMullen AR, Wilen CB, Burnham CAD. Epidemiology of Blood Stream Infections in the Dark Art of Blood Culture.  Dunne M and Burnham CAD, Editors. ASM press. (2018). Link


Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. Norovirus cell tropism is determined by combinatorial action of a viral non-structural protein and host cytokine. Cell Host & Microbe. (2017) Oct 11. Pubmed


Biering SB,Choi J, Halstrom RA, Brown HM, Beatty WL, Lee S, McCune BT, Dominici E, Williams LE, Orchard RC, Wilen CB, Yamamoto M, Coers J, Taylor GA, and Hwang S. Viral replication complexes are targeted by LC3-guided interferon-inducible GTPases. Cell Host & Microbe. (2017) Jul 12;22(1):74-85. Pubmed


Wilen CB, Booth GS, Grossman BJ, Lane WJ, Szlarski PC, Jackups R. Using direct antiglobulin test results to reduce unnecessary cold agglutinin testing. Transfusion.(2017) Mar 7; 57(6): 1480-4. Pubmed


Orchard RC*, Wilen CB*, Doench JG, Baldridge MT, McCune BT, Lee YJ, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, and Virgin HW. Discovery of a proteinaceous cellular receptor for a norovirus. Science. (2016): 353(6302):933-6. Pubmed


O’Brien M, Manches O, Wilen CB, Wu V, Sunseri N, Bhardwaj N. CD4 receptor is key determinant of divergent HIV-1 sensing by plasmacytoid dendritic cells (2016) PLoSPathogens. (2016) Apr 15;12(4)e1005553. Pubmed


Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova, Wilen CB, Orchard RC, Virgin HW, Listgarten J, and Root DE.  Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nature Biotechnology. (2016) 34(2):184-91. Pubmed


Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, Lankowski A, Baldridge MT, Wilen CB, Flagg M, Norman JM, Keller BC, Levano JM, Wang D, Boum Y, Martin JN, Hunt PW, Bangsberg DR, Siedner MJ, Kown DS, and Virgin HW. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-associated Acquired Immunodeficiency Syndrome. Cell Host & Microbe(2016) 19(3): 311-22. Pubmed


Lu Q, Yokoyama CC, Williams JW, Baldridge MT, Jin X, DesRochers B, Bricker T, Wilen CB, Bagaitkar J, Loginicheva E, Sergushichev A, Kreamalmeyer D, Keller BC, Zhao Y, Kambal A, Green DG, Martinez J, Dinauer MC, Holtzman MJ, Crouch EC, Beatty W, Boon ACM, Zhang H, Randolph GJ, Artyomov MN, and Virgin HW. Homeostatic control of innate immune lung inflammation by Vici syndrome gene Epg5and additional autophagy genes promotes influenza virus pathogenesis.  Cell Host & Microbe(2016) 19(1):102-13. Pubmed


Gonzalez MD*, Wilen CB*, and Burnham CAD. Markers of intestinal inflammation for the diagnosis of infectious gastroenteritis. (2015) Clin Lab Med. 34(2): 333-44. Pubmed

Wilen CB, McMullen AR, and Burnham CAD. Comparison of sample preparation methods, instrumentation platforms, and contemporary commercial databases for identification of clinically relevant mycobacteria by matrix-assisted laser desorption ionization-time of flight mass spectrometry. (2015) J Clin Micro. 53(7): 2308-15. Pubmed

Wilen CB, Szymanski JJ, Hung S, Rajan A, Lavigne PM, Char DM, Geltman EM, and Scott MG. The impact on patient management and outcome of switching between two contemporary sensitive cardiac troponin assays. (2015) Clin Chem. 61(6):870-6. Pubmed

Wilen CB, Monaco CM, Hoppe-Bauer J, Jackups R, Bucelli RC, Burnham CAD.  Criteria to reduce unnecessary testing for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and enterovirus in cerebrospinal fluid samples from adults. (2015) J Clin Micro.52(3): 887-95.  Pubmed


Wilen CB, Orner C, Brown SM. Sustaining Point of Care Testing in a Resource-Limited Environment: Experiences in Hispaniola, in Global Point-of-Care Strategies for Disasters, Complex Emergencies, and Public Health Crises: Enhancing Standards of Care at the Site of Need.Kost GJ and Curtis CM, editors. 2014, AACC Press: Washington, DC.

Petersen J*, Drake MJ*, Bruce EA*, Riblett AM, Didigu CA, Wilen CB, Malani N, Male F, Lee FH, Bushman FD, Cherry S, Doms RW, Bates P, Briley K Jr. The major cellular sterol regulatory pathway is required for andes virus infection. (2014) PLoS Pathogens 10(2):e1003911. Pubmed

Didigu CA, Wilen CB, Wang J, Duong J, Secreto AJ, Danet-Desnoyers GA, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. (2014) Blood123(1): 61-9. Pubmed


Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, Zajic L, Iyer SS, Decker JM, Kumar A, Hora B, Berg A, Cai F, Hopper J, Denny TN, Ding H, Ochsenbauer C, Kappes JC, Galimidi RP, West AP Jr, Bjorkman PJ, Wilen CB, Doms RW, O'Brien M, Bhardwaj N, Borrow P, Haynes BF, Muldoon M, Theiler JP, Korber B, Shaw GM, Hahn BH. Phenotypic properties of transmitted founder HIV-1.  (2013) Proc Natl Aca Sci110(17):6626-33.  Pubmed

Parker ZF*, Iyer SS*, Wilen CB, Parrish NF, Chikere KC, Lee F, Didigu CA, Berro R, Klasse PJ, Lee B, Moore JP, Shaw GM, Hahn BH, and Doms RW. Transmitted/Founder and Chronic HIV-1 Envelope Proteins are Distinguished by Differential Utilization of CCR5. (2013) J Virol 87(5):2401-11. Pubmed


Parrish NF*, Wilen CB*, Banks L, Iyer S, Pfaff JM, Salazar-Gonzalez JF, Salazar MG, Decker JM, Parrish EH, Berg A, Hopper J, Kumar A, Mahlokozera T, Yuan S, Coleman C, Vermeulen M, Ochsenbauer C, Tilton JC, Permar SR, Kappes JC, Betts MR, Busch MP, Gao F, Montefiori D, Haynes BF, Shaw GM, Hahn BH, Doms RW.  Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.  (2012) PLoS Pathogens. 8(5):e1002686. Pubmed

Wilen CB, Tilton JC, Doms RW.  HIV: cell binding and entry, in Human Immunodeficiency Virus. FD Bushman, G Nabel, and R Swanstrom, Editors. 2012, Cold Spring Harbor: Cold Spring Laboratory Press:  Cold Spring Harbor, NY. Pubmed

Wilen CB, Tilton JC, and Doms RW.  Molecular mechanisms of HIV entry, in Viral Molecular Machines, M. Rossman and V. Rao, Editors. 2012, Springer-Verlag: New York, NY. Pubmed


Jiang C*, Parrish N*, Wilen CB*, Li H*, Chen Y, Pavlicek JW, Berg A, Tomaras G, Tilton JC, Decker JM, Haynes BF, Shaw GM, Doms RW, Hahn BH, Gao F. Primary infection by a human immunodeficiency virus with atypical coreceptor tropism. (2011) J Virol 85(20):10669-81Pubmed

Wilen CB*, Parrish N*, Pfaff JM, Decker JM, Henning EA, Haynes BF, Tilton JC, Shaw GM, Hahn BH, Doms RW. Phenotypic comparison of clade B transmitted/founder and chronic HIV-1 Envs. (2011) J Virol 85(17):8514-27.Pubmed

Wilen CB, Wang J, Tilton JC, Miller JC, Kim KA, Rebar EJ, Sherrill-Mix SA, Patro SC, Secreto AJ, Jordan APO, Lee G, Kahn J, Aye PP, Bunnell BA, Lackner AA, Hoxie JA, Danet-Desnoyers GA, Bushman FD, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc finger nucleases. (2011) Plos Pathogens7(4):e1002020. Pubmed


Tilton, JC, Wilen CB, Didigu C, Sinha R, Harrison J, Agrawal-Gamse C, Henning E, Bushman FD, Deeks SD, Doms RW.  A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5. (2010) J Virol 84(20):10863-76.Pubmed

Leung W, Shaffer CD, Cordonnier T, Wong J, Itano MS, Slawson Tempel EE, Kellmann E, Desruisseau DM, Cain C, Carrasquillo R, Chusak TM, Falkowska K, Grim KD, Guan R, Honeybourne J, Khan S, Lo L, McGaha R, Plunkett J, Richner JM, Richt R, Sabin L, Shah A, Sharma A, Singhal S, Song F, Swope C, Wilen CB, Buhler J, Mardis ER, Elgin SC. Evolution of a distinct genomic domain in Drosophila: comparative analysis of the dot chromosome in Drosophila melanogaster and Drosophila virilis. (2010) Genetics 185(4):1519-34. Pubmed

Pfaff JM, Wilen CB, Harrison JE, Demarest JF, Lee B, Doms RW, Tilton JC.  HIV-1 resistance to CCR5 antagonists associated with highly efficient use of CCR5 and altered tropism on primary CD4+ T cells. (2010) J Virol. 84(13):6505-14. Pubmed

*These authors contributed equally