Susan Zolla-Pazner

Susan Zolla-Pazner is an American research scientist who is a Professor of Medicine in the Division of Infectious Diseases and the Department of Microbiology at Mount Sinai School of Medicine and a guest investigator in the Laboratory of Molecular Immunology at The Rockefeller University,[1] both in New York City. Zolla-Pazner's work has focused on how the immune system responds to the human immunodeficiency virus (HIV) and, in particular, how antibodies against the viral envelope develop in the course of infection.

Susan Zolla-Pazner

In 1981, Zolla-Pazner and other researchers initially described the immunologic abnormalities afflicting homosexual men in New York City who were dying from an unknown sickness.[2] In the years since, she has examined the body's immune response to the virus.[3] She is the co-inventor on 23 patents[4] and the author of more than 325 scientific publications.[5]

Research

Zolla-Pazner’s work helped establish the central role of antibodies in protection from HIV infection. She proposed quantifying the antibodies directed at the second and third variable loops (V2 and V3) of the HIV envelope protein gp120,[6][7][8][9] [10] [11] [12] as observed in the Phase 3 RV144 clinical HIV vaccine trial, which involved 16,402 participants in Thailand.[13] Her research indicated that high levels of antibodies to V2 correlated with a reduced rate of infection.[14] Antibodies to V3 were subsequently identified as an additional correlate of protection exerting immune pressure on viruses infecting individuals who had received the vaccine.[15] Zolla-Pazner's research indicated that the search for an effective vaccine should focus not only on inducing specific types of antibodies but on eliciting a durable antibody response, as post-hoc analysis showed the antibodies in diminishing amounts from year 1 to year 3.[16] Her findings established the key role of antibodies specific for the virus envelope's variable regions in protection from HIV infection; they also validated her hypothesis that antibodies to variable regions could be protective—a highly controversial point until then.

In the early days of the AIDS epidemic, the Zolla-Pazner lab described the hyperactivation of B lymphocytes in the blood of HIV-infected individuals.[17][18][19][20] This discovery led her to develop methods to generate anti-HIV human monoclonal antibodies (mAbs) from the blood cells of HIV-infected individuals.[6][7][21] Her lab isolated and described human mAbs capable of neutralizing the infectivity of the virus,[6][21][22] and, later, isolated a mAb with strong neutralizing potency targeting a complex epitope composed of V2 and V3.[23][24][25][26] Her lab also described how antibodies to V2 and V3 could bind and neutralize viruses from all over the globe, despite extreme variations in amino acid sequences.[7][27][28][29][30][31][32][33][34][35]

In 1981, Zolla-Pazner participated in the description of the immunologic abnormalities of patients presenting with Kaposi’s sarcoma, which was associated with the then-mysterious illness that later became known as AIDS.[36] She initiated systemic testing to enumerate CD4 and CD8 cells and antibodies in order to diagnose HIV infection and follow the effects of treatment with antiretroviral drugs. She was also responsible for the description of immunologic abnormalities in the first patients with AIDS-related Mycobacterium avium-intracellulare infections[37] and for identifying similar immunologic abnormalities in apparently healthy gay men who later developed AIDS.[38] This latter work was an early indication of the chilling reality that one-third of gay men in New York City were suffering from this fatal but as-yet-unidentified illness. In 1989, Zolla-Pazner became Director of AIDS Research at the Manhattan Veterans Administration Medical Center,[39][40] part of the NYU School of Medicine,[41][42][43][44] where she was a member of the Department of Pathology[45] for 46 years. In 2015, Zolla-Pazner moved to Mount Sinai School of Medicine.

Building on her correlation of levels of V2 antibodies with reduced infection rates in the RV144 vaccine trial, Zolla-Pazner and her colleagues have spent the last 10 years developing “designer vaccines,” i.e., V2- and V3-scaffold proteins that focus the immune response on the production of antibodies specific for these two regions of gp120.[46][47] Studies of these recombinant vaccine constructs in both rabbits and nonhuman primates have demonstrated that they induce antibodies that react with the envelopes of diverse viruses within the various subgroups of HIV and have biologic activities that have been associated with protection from infection.[12][48][49]

gollark: Might work.
gollark: But 3D.
gollark: <:enderium:501019552004702242> <:beryllium:501019257329549333> <:enderium:501019552004702242> <:beryllium:501019257329549333> <:cell:501019302116327427> <:beryllium:501019257329549333> <:enderium:501019552004702242> <:beryllium:501019257329549333> <:enderium:501019552004702242>
gollark: A fusion reactor!
gollark: Do you actually *need* or even want full type inference?

References
  1. "Mount Sinai Profiles". Mount Sinai.
  2. "LaGuardia and Wagner Archives, Koch Oral History Collection- Koch Scholars interview, Dr. Michael Simberkoff_04-07-2015" (PDF). La Guardia and Wagner Archives (Koch Oral History Collection, Koch Scholars interview). April 7, 2015. p. 3. Retrieved 2017-03-31.
  3. Miley, Marissa (2012-10-15). "Susan-Zolla Pazner is an antibody person". AAAS - The World's Largest General Scientific Society. Retrieved 2017-03-30.
  4. "Wipo Publishes Patent of New York University School of Medicine, Timothy Cardozo, Kong Xiangpeng and Susan Zolla-Pazner for "Peptides Mimicking HIV-1 Viral Epitopes in the V2 Loop for the Gp120 Surface Envelope Glycoprotein" (American Inventors)". HighBeam Research. US Fed News Service, Including US State New. News Wire. March 25, 2013. Archived from the original on November 17, 2018. Retrieved March 23, 2017.
  5. "Susan Zolla-Pazner - Google Scholar". scholar.google.com. Retrieved 2017-04-19.
  6. Gorny, M. K.; Xu, J. Y.; Gianakakos, V.; Karwowska, S.; Williams, C.; Sheppard, H. W.; Hanson, C. V.; Zolla-Pazner, S. (1991-04-15). "Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein". Proc Natl Acad Sci U S A. 88 (8): 3238–3242. doi:10.1073/pnas.88.8.3238. ISSN 0027-8424. PMC 51421. PMID 2014246.
  7. Gorny, MK; Moore, JP; Conley, A J; Karwowska, S; Sodroski, J; Williams, C; Burda, S; Boots, LJ; Zolla-Pazner, S (1994-12-01). "Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1". J Virol. 68 (12): 8312–8320. ISSN 0022-538X. PMC 237300. PMID 7525987.
  8. Pinter, A; Honnen, WJ; He, Y; Gorny, MK; Zolla-Pazner, S; Kayman, SC (2004-05-01). "The V1/V2 domain of gp120 is a global regulator of the sensitivity of primary human immunodeficiency virus type 1 isolates to neutralization by antibodies commonly induced upon infection". J Virol. 78 (10): 5205–5215. doi:10.1128/JVI.78.10.5205-5215.2004. ISSN 0022-538X. PMC 400352. PMID 15113902.
  9. Burke, V; Williams, C; Sukumaran, M; Kim, S-S; Li, H; Wang, XH; Gorny, MK; Zolla-Pazner, S; Kong, X-P (2009-11-11). "Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens". Structure. 17 (11): 1538–1546. doi:10.1016/j.str.2009.09.012. ISSN 1878-4186. PMC 3683248. PMID 19913488.
  10. Jiang, X; Burke, V; Totrov, M; Williams, C; Cardozo, T; Gorny, MK; Zolla-Pazner, S; Kong, X-P (2010). "Conserved structural elements in the V3 crown of HIV-1 gp120". Nat Struct Mol Biol. 17 (8): 955–961. doi:10.1038/nsmb.1861. PMID 20622876.
  11. Pan, R; Gorny, MK; Zolla-Pazner, S; Kong, X-P (2015-08-01). "The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel". J Virol. 89 (15): 8003–8010. doi:10.1128/JVI.00754-15. ISSN 0022-538X. PMC 4505664. PMID 26018158.
  12. Zolla-Pazner, S; Cohen, SS; Boyd, D; Kong, X-P; Seaman, M; Nussenzweig, M; Klein, F; Overbaugh, J; Totrov, M (2015-10-21). "Structure/Function Studies Involving the V3 Region of the HIV-1 Envelope Delineate Multiple Factors That Affect Neutralization Sensitivity". J Virol. 90 (2): 636–649. doi:10.1128/JVI.01645-15. ISSN 1098-5514. PMC 4702699. PMID 26491157.
  13. Rerks-Ngarm, S; Pitisuttithum, P; Nitayaphan, S; Kaewkungwal, J; Chiu, J; Paris, R; Premsri, N; Namwat, C; de Souza, M (2009-12-03). "Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand". N Engl J Med. 361 (23): 2209–2220. doi:10.1056/NEJMoa0908492. ISSN 0028-4793. PMID 19843557.
  14. Haynes, Barton F.; Gilbert, Peter B.; McElrath, M. Juliana; Zolla-Pazner, Susan; Tomaras, Georgia D.; Alam, S. Munir; Evans, David T.; Montefiori, David C.; Karnasuta, Chitraporn (2012). "Immune-correlates analysis of an HIV-1 vaccine efficacy trial". The New England Journal of Medicine. 366 (14): 1275–1286. doi:10.1056/NEJMoa1113425. ISSN 1533-4406. PMC 3371689. PMID 22475592.
  15. Gottardo, Raphael; Bailer, Robert T.; Korber, Bette T.; Gnanakaran, S.; Phillips, Joshua; Shen, Xiaoying; Tomaras, Georgia D.; Turk, Ellen; Imholte, Gregory; Eckler, Larry; Wenschuh, Holger; Zerweck, Johannes; Greene, Kelli; Gao, Hongmei; Berman, Phillip W.; Francis, Donald; Sinangil, Faruk; Lee, Carter; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Tartaglia, James; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Zolla-Pazner, Susan; Haynes, Barton F.; Mascola, John R.; Self, Steve; Gilbert, Peter; Montefiori, David C. (2013). "Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial". PLOS ONE. 8 (9): e75665. doi:10.1371/journal.pone.0075665. ISSN 1932-6203. PMC 3784573. PMID 24086607.
  16. Karasavvas, N; Billings, E; Rao, M; Williams, C; Zolla-Pazner, S; Bailer, RT; Koup, RA; Madnote, S; Arworn, D (2012-11-01). "The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120". AIDS Res Hum Retroviruses. 28 (11): 1444–1457. doi:10.1089/aid.2012.0103. ISSN 1931-8405. PMC 3484815. PMID 23035746.
  17. Zolla-Pazner, Susan; Sidhu, G, eds. (1983). The possible pathogenic role of hyperactive B lymphocytes in AIDS. New York, NY: A Friedman Kien Masson Publications.
  18. Mizuma, H.; Zolla-Pazner, S.; Litwin, S.; el-Sadr, W.; Sharpe, S.; Zehr, B.; Weiss, S.; Saxinger, W. C.; Marmor, M. (1987-04-01). "Serum IgD elevation is an early marker of B cell activation during infection with the human immunodeficiency viruses". Clinical and Experimental Immunology. 68 (1): 5–14. ISSN 0009-9104. PMC 1542677. PMID 3498566.
  19. Mizuma, H.; Litwin, S.; Zolla-Pazner, S. (1988-03-01). "B-cell activation in HIV infection: relationship of spontaneous immunoglobulin secretion to various immunological parameters". Clinical and Experimental Immunology. 71 (3): 410–416. ISSN 0009-9104. PMC 1541680. PMID 3260155.
  20. Edelman, A. S.; Zolla-Pazner, S. (1989-01-01). "AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency". FASEB Journal. 3 (1): 22–30. doi:10.1096/fasebj.3.1.2562947. ISSN 0892-6638. PMID 2562947.
  21. Gorny, M. K.; Gianakakos, V.; Sharpe, S.; Zolla-Pazner, S. (1989-03-01). "Generation of human monoclonal antibodies to human immunodeficiency virus". Proceedings of the National Academy of Sciences of the United States of America. 86 (5): 1624–1628. doi:10.1073/pnas.86.5.1624. ISSN 0027-8424. PMC 286751. PMID 2922401.
  22. Conley, A. J.; Gorny, M. K.; Kessler, J. A.; Boots, L. J.; Ossorio-Castro, M.; Koenig, S.; Lineberger, D. W.; Emini, E. A.; Williams, C; Zolla-Pazner, S (1994). "Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D". Journal of Virology. 68 (11): 6994–7000. ISSN 0022-538X. PMC 237136. PMID 7933081.
  23. Gorny, Miroslaw K.; Stamatatos, Leonidas; Volsky, Barbara; Revesz, Kathy; Williams, Constance; Wang, Xiao-Hong; Cohen, Sandra; Staudinger, Robert; Zolla-Pazner, Susan (2005-04-01). "Identification of a new quaternary neutralizing epitope on human immunodeficiency virus type 1 virus particles". Journal of Virology. 79 (8): 5232–5237. doi:10.1128/JVI.79.8.5232-5237.2005. ISSN 0022-538X. PMC 1069558. PMID 15795308.
  24. Honnen, W. J.; Krachmarov, C.; Kayman, S. C.; Gorny, M. K.; Zolla-Pazner, S.; Pinter, A. (February 1, 2001). "Type-specific epitopes targeted by monoclonal antibodies with exceptionally potent neutralizing activities for selected strains of human immunodeficiency virus type 1 map to a common region of the V2 domain of gp120 and differ only at single positions from the clade B consensus sequence". J Virol. 81 (3): 1424–1432. doi:10.1128/JVI.02054-06. ISSN 0022-538X. PMC 1797533. PMID 17121806.
  25. Changela, Anita; Wu, Xueling; Yang, Yongping; Zhang, Baoshan; Zhu, Jiang; Nardone, Glenn A.; O'Dell, Sijy; Pancera, Marie; Gorny, Miroslaw K; Zolla-Pazner, S; Mascola, JR; Kwong, PD (2011-03-01). "Crystal structure of human antibody 2909 reveals conserved features of quaternary structure-specific antibodies that potently neutralize HIV-1". Journal of Virology. 85 (6): 2524–2535. doi:10.1128/JVI.02335-10. ISSN 1098-5514. PMC 67962. PMID 21191009.
  26. Wu, Xueling; Changela, Anita; O'Dell, Sijy; Schmidt, Stephen D.; Pancera, Marie; Yang, Yongping; Zhang, Baoshan; Gorny, Miroslaw K.; Phogat, Sanjay; Robinson, James E.; Stamatatos, Leonidas; Zolla-Pazner, Susan; Kwong, Peter D.; Mascola, John R. (2011-05-01). "Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies". Journal of Virology. 85 (9): 4578–4585. doi:10.1128/JVI.02585-10. ISSN 0022-538X. PMC 3126226. PMID 21325411.
  27. Gorny, M. K.; VanCott, T. C.; Hioe, C.; Israel, Z. R.; Michael, N. L.; Conley, A. J.; Williams, C.; Kessler, J. A.; Chigurupati, P.; Burda, S.; Zolla-Pazner, S. (1997-11-15). "Human monoclonal antibodies to the V3 loop of HIV-1 with intra- and interclade cross-reactivity". Journal of Immunology. 159 (10): 5114–5122. ISSN 0022-1767. PMID 9366441.
  28. Gorny, M. K.; Mascola, J. R.; Israel, Z. R.; VanCott, T. C.; Williams, C.; Balfe, P.; Hioe, C.; Brodine, S.; Burda, S.; Zolla-Pazner, S. (1998-02-10). "A human monoclonal antibody specific for the V3 loop of HIV type 1 clade E cross-reacts with other HIV type 1 clades". AIDS Research and Human Retroviruses. 14 (3): 213–221. doi:10.1089/aid.1998.14.213. ISSN 0889-2229. PMID 9491911.
  29. Nyambi, P. N.; Gorny, M. K.; Bastiani, L.; van der Groen, G.; Williams, C.; Zolla-Pazner, S. (1998-11-01). "Mapping of epitopes exposed on intact human immunodeficiency virus type 1 (HIV-1) virions: a new strategy for studying the immunologic relatedness of HIV-1". Journal of Virology. 72 (11): 9384–9391. ISSN 0022-538X. PMC 110366. PMID 9765494.
  30. Nyambi, P. N.; Mbah, H. A.; Burda, S.; Williams, C.; Gorny, M. K.; Nádas, A.; Zolla-Pazner, S. (2000-08-01). "Conserved and exposed epitopes on intact, native, primary human immunodeficiency virus type 1 virions of group M". Journal of Virology. 74 (15): 7096–7107. doi:10.1128/JVI.74.15.7096-7107.2000. ISSN 0022-538X. PMC 112228. PMID 10888650.
  31. Gorny, MK; Williams, C; Volsky, B; Revesz, K; Cohen, S; Polonis, Victoria R.; Honnen, WJ; Kayman, SC; Krachmarov, C; Pinter, A; Zolla-Pazner, S (2002-09-01). "Human monoclonal antibodies specific for conformation-sensitive epitopes of V3 neutralize human immunodeficiency virus type 1 primary isolates from various clades". Journal of Virology. 76 (18): 9035–9045. doi:10.1128/JVI.76.18.9035-9045.2002. ISSN 0022-538X. PMC 136433. PMID 12186887.
  32. Gorny, Miroslaw K.; Williams, Constance; Volsky, Barbara; Revesz, Kathy; Wang, Xiao-Hong; Burda, Sherri; Kimura, Tetsuya; Konings, Frank A. J.; Nádas, Arthur; Anyangwe, CA; Nyambi, P; Krachmarov, C; Pinter, A; Zolla-Pazner, S (2006-07-01). "Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1". Journal of Virology. 80 (14): 6865–6872. doi:10.1128/JVI.02202-05. ISSN 0022-538X. PMC 1489067. PMID 16809292.
  33. Hioe, Catarina E.; Wrin, Terri; Seaman, Michael S.; Yu, Xuesong; Wood, Blake; Self, Steve; Williams, Constance; Gorny, Miroslaw K.; Zolla-Pazner, Susan (2010-04-21). "Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes". PLOS ONE. 5 (4): e10254. doi:10.1371/journal.pone.0010254. ISSN 1932-6203. PMC 2858080. PMID 20421997.
  34. Gorny, Miroslaw K.; Pan, Ruimin; Williams, Constance; Wang, Xiao-Hong; Volsky, Barbara; O'Neal, Timothy; Spurrier, Brett; Sampson, Jared M.; Li, Liuzhe; Kong, XP; Zolla-Pazner, Susan (2012-06-05). "Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals". Virology. 427 (2): 198–207. doi:10.1016/j.virol.2012.02.003. ISSN 1096-0341. PMC 3572902. PMID 22402248.
  35. deCamp, Allan; Hraber, Peter; Bailer, Robert T.; Seaman, Michael S.; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, H; Greene, K; Gao, H; Daniell, X; Sarzotti-Kelsoe, M; Gorny, MK; Zolla-Pazner, S; LaBranche, CC; Mascola, JR; Korber, BT; Montefiori, CD (2014-03-01). "Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies". Journal of Virology. 88 (5): 2489–2507. doi:10.1128/JVI.02853-13. ISSN 1098-5514. PMC 3958090. PMID 24352443.
  36. Friedman-Kien, A. E.; Laubenstein, L. J.; Rubinstein, P.; Buimovici-Klein, E.; Marmor, M.; Stahl, R.; Spigland, I.; Kim, K. S.; Zolla-Pazner, S. (1982-06-01). "Disseminated Kaposi's sarcoma in homosexual men". Annals of Internal Medicine. 96 (6 Pt 1): 693–700. doi:10.7326/0003-4819-96-6-693. ISSN 0003-4819. PMID 6283973.
  37. Greene, J. B.; Sidhu, G. S.; Lewin, S.; Levine, J. F.; Masur, H.; Simberkoff, M. S.; Nicholas, P.; Good, R. C.; Zolla-Pazner, S. B. (1982-10-01). "Mycobacterium avium-intracellulare: a cause of disseminated life-threatening infection in homosexuals and drug abusers". Annals of Internal Medicine. 97 (4): 539–546. doi:10.7326/0003-4819-97-4-539. ISSN 0003-4819. PMID 6289714.
  38. Stahl, R. E.; Friedman-Kien, A.; Dubin, R.; Marmor, M.; Zolla-Pazner, S. (1982-08-01). "Immunologic abnormalities in homosexual men. Relationship to Kaposi's sarcoma". The American Journal of Medicine. 73 (2): 171–178. doi:10.1016/0002-9343(82)90174-7. ISSN 0002-9343. PMID 7114072.
  39. System, VA NY Harbor Healthcare. "VA NY Harbor Health Care System". www.nyharbor.va.gov. Retrieved 2017-05-09.
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  43. Carey, Benedict (November 5, 2012). "A Collective Effort to Save Decades of Research as the Water Tose". The New York Times. Retrieved March 23, 2017.
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  46. Totrov, Maxim; Jiang, Xunqing; Kong, Xiang-Peng; Cohen, Sandra; Krachmarov, Chavdar; Salomon, Aidy; Williams, Constance; Seaman, Michael S.; Abagyan, Ruben; Cardozo, T; Gorny, MK; Wang, S; Lu, S; Pinter, A; Zolla-Pazner, S (2010-09-30). "Structure-guided design and immunological characterization of immunogens presenting the HIV-1 gp120 V3 loop on a CTB scaffold". Virology. 405 (2): 513–523. doi:10.1016/j.virol.2010.06.027. ISSN 1096-0341. PMC 2942080. PMID 20663531.
  47. Spurrier, Brett; Sampson, Jared M.; Totrov, Maxim; Li, Huiguang; O'Neal, Timothy; Williams, Constance; Robinson, James; Gorny, Miroslaw K.; Zolla-Pazner, Susan (2011-05-11). "Structural analysis of human and macaque mAbs 2909 and 2.5B: implications for the configuration of the quaternary neutralizing epitope of HIV-1 gp120". Structure. 19 (5): 691–699. doi:10.1016/j.str.2011.02.012. ISSN 1878-4186. PMC 3096878. PMID 21565703.
  48. Zolla-Pazner, Susan; Kong, X.-P.; Jiang, Xunqing; Cardozo, Timothy; Nádas, Arthur; Cohen, Sandra; Totrov, Maxim; Seaman, Michael S.; Wang, Shixia (2011-10-01). "Cross-clade HIV-1 neutralizing antibodies induced with V3-scaffold protein immunogens following priming with gp120 DNA". Journal of Virology. 85 (19): 9887–9898. doi:10.1128/JVI.05086-11. ISSN 1098-5514. PMC 3196418. PMID 21795338.
  49. Zolla-Pazner, Susan; Powell, Rebecca; Yahyaei, Sara; Williams, Constance; Jiang, Xunqing; Li, Wei; Lu, Shan; Wang, Shixia; Upadhyay, Chitra (2016-12-15). "Rationally Designed Vaccines Targeting the V2 Region of HIV-1 gp120 Induce a Focused, Cross-Clade-Reactive, Biologically Functional Antibody Response". Journal of Virology. 90 (24): 10993–11006. doi:10.1128/JVI.01403-16. ISSN 1098-5514. PMC 5126359. PMID 27630234.
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