HIV-1 Nef is carried on the surface of extracellular vesicles.


Journal

Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479

Informations de publication

Date de publication:
Jul 2024
Historique:
revised: 11 05 2024
received: 29 12 2023
accepted: 17 06 2024
medline: 17 7 2024
pubmed: 17 7 2024
entrez: 17 7 2024
Statut: ppublish

Résumé

Extracellular vesicles (EVs) serve as pivotal mediators of intercellular communication in both health and disease, delivering biologically active molecules from vesicle-producing cells to recipient cells. In the context of HIV infection, EVs have been shown to carry the viral protein Nef, a key pathogenic factor associated with HIV-related co-morbidities. Despite this recognition, the specific localisation of Nef within the vesicles has remained elusive. This study addresses this critical knowledge gap by investigating Nef-containing EVs. Less than 1% of the total released Nef was associated with EVs; most Nef existed as free protein released by damaged cells. Nevertheless, activity of EV-associated Nef in downregulating the major cholesterol transporter ABCA1, a critical aspect linked to the pathogenic effects of Nef, was comparable to that of free Nef present in the supernatant. Through a series of biochemical and microscopic assays, we demonstrate that the majority of EV-associated Nef molecules are localised on the external surface of the vesicles. This distinctive distribution prompts the consideration of Nef-containing EVs as potential targets for immunotherapeutic interventions aimed at preventing or treating HIV-associated co-morbidities. In conclusion, our results shed light on the localisation and functional activity of Nef within EVs, providing valuable insights for the development of targeted immunotherapies to mitigate the impact of HIV-associated co-morbidities.

Identifiants

pubmed: 39016173
doi: 10.1002/jev2.12478
doi:

Substances chimiques

nef Gene Products, Human Immunodeficiency Virus 0
nef protein, Human immunodeficiency virus 1 0
ATP Binding Cassette Transporter 1 0
ABCA1 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e12478

Subventions

Organisme : Intramural NIH HHS
ID : ZIA HD008998
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL158305
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS124477
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI117970
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI172028
Pays : United States

Informations de copyright

© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

Références

Aiken, C., Konner, J., Landau, N. R., Lenburg, M. E., & Trono, D. (1994). Nef induces CD4 endocytosis: Requirement for a critical dileucine motif in the membrane‐proximal CD4 cytoplasmic domain. Cell, 76, 853–864.
Arakelyan, A., Fitzgerald, W., Margolis, L., & Grivel, J. C. (2013). Nanoparticle‐based flow virometry for the analysis of individual virions. Journal of Clinical Investigation, 123, 3716–3727.
Bachurski, D., Schuldner, M., Nguyen, P. H., Malz, A., Reiners, K. S., Grenzi, P. C., Babatz, F., Schauss, A. C., Hansen, H. P., Hallek, M., & Pogge von Strandmann, E. (2019). Extracellular vesicle measurements with nanoparticle tracking analysis—An accuracy and repeatability comparison between NanoSight NS300 and ZetaView. Journal of Extracellular Vesicles, 8, 1596016.
Buffalo, C. Z., Iwamoto, Y., Hurley, J. H., & Ren, X. (2019). How HIV Nef proteins hijack membrane traffic to promote infection. Journal of Virology, 93, e01322‐e01319.
Burdo, T. H., Lo, J., Abbara, S., Wei, J., DeLelys, M. E., Preffer, F., Rosenberg, E. S., Williams, K. C., & Grinspoon, S. (2011). Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV‐infected patients. Journal of Infectious Diseases, 204, 1227–1236.
Chelvanambi, S., Gupta, S. K., Chen, X., Ellis, B. W., Maier, B. F., Colbert, T. M., Kuriakose, J., Zorlutuna, P., Jolicoeur, P., Obukhov, A. G., & Clauss, M. (2019). HIV‐Nef protein transfer to endothelial cells requires Rac1 activation and leads to endothelial dysfunction implications for statin treatment in HIV patients. Circulation Research, 125, 805–820.
Consortium, E.‐T., Van Deun, J., Mestdagh, P., Agostinis, P., Akay, O., Anand, S., Anckaert, J., Martinez, Z. A., Baetens, T., Beghein, E., Bertier, L., Berx, G., Boere, J., Boukouris, S., Bremer, M., Buschmann, D., Byrd, J. B., Casert, C., Cheng, L., … Hendrix, A. (2017). EV‐TRACK: Transparent reporting and centralizing knowledge in extracellular vesicle research. Nature Methods, 14, 228–232.
Corro, G., Crudeli, C. M., Rocco, C. A., Marino, S. A., & Sen, L. (2014). High levels of anti‐Nef antibodies may prevent AIDS disease progression in vertically HIV‐1‐infected infants. Journal of the International AIDS Society, 17, 18790.
Cvjetkovic, A., Jang, S. C., Konecna, B., Hoog, J. L., Sihlbom, C., Lasser, C., & Lotvall, J. (2016). Detailed analysis of protein topology of extracellular vesicles‐evidence of unconventional membrane protein orientation. Scientific Reports, 6, 36338.
da Silva‐Januario, M. E., da Costa, C. S., Tavares, L. A., Oliveira, A. K., Januario, Y. C., de Carvalho, A. N., Cassiano, M. H. A., Rodrigues, R. L., Miller, M. E., Palameta, S., Arns, C. W., Arruda, E., Paes Leme, A. F., & daSilva, L. L. P. (2023). HIV‐1 Nef changes the proteome of T cells extracellular vesicles depleting IFITMs and other antiviral factors. Molecular & Cellular Proteomics, 22, 100676.
Dennis, C. A., Baron, A., Grossmann, J. G., Mazaleyrat, S., Harris, M., & Jaeger, J. (2005). Co‐translational myristoylation alters the quaternary structure of HIV‐1 Nef in solution. Proteins, 60, 658–669.
Ditiatkovski, M., Mukhamedova, N., Dragoljevic, D., Hoang, A., Low, H., Pushkarsky, T., Fu, Y., Carmichael, I., Hill, A. F., Murphy, A. J., Bukrinsky, M., & Sviridov, D. (2020). Modification of lipid rafts by extracellular vesicles carrying HIV‐1 protein Nef induces redistribution of APP and Tau causing neuronal dysfunction. Journal of Biological Chemistry, 295, 13377–13392.
Dubrovsky, L., Ward, A., Choi, S. H., Pushkarsky, T., Brichacek, B., Vanpouille, C., Adzhubei, A. A., Mukhamedova, N., Sviridov, D., Margolis, L., Jones, R. B., Miller, Y. I., & Bukrinsky, M. (2020). Inhibition of HIV replication by apolipoprotein A‐I binding protein targeting the lipid rafts. MBio, 11, e02956‐e02919.
Ferdin, J., Goricar, K., Dolzan, V., Plemenitas, A., Martin, J. N., Peterlin, B. M., Deeks, S. G., & Lenassi, M. (2018). Viral protein Nef is detected in plasma of half of HIV‐infected adults with undetectable plasma HIV RNA. PLoS ONE, 13, e0191613.
Fitzgerald, W., Freeman, M. L., Lederman, M. M., Vasilieva, E., Romero, R., & Margolis, L. (2018). A system of cytokines encapsulated in extracellular vesicles. Scientific Reports, 8, 8973.
Fujii, Y., Otake, K., Tashiro, M., & Adachi, A. (1996). Soluble Nef antigen of HIV‐1 is cytotoxic for human CD4+ T cells. Febs Letters, 393, 93–96.
Gao, F., Li, Y., Decker, J. M., Peyerl, F. W., Bibollet‐Ruche, F., Rodenburg, C. M., Chen, Y., Shaw, D. R., Allen, S., Musonda, R., Shaw, G. M., Zajac, A. J., Letvin, N., & Hahn, B. H. (2003). Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: In vitro expression and immune responses in DNA‐vaccinated mice. Aids Research and Human Retroviruses, 19, 817–823.
Gendelman, H. E., Orenstein, J. M., Martin, M. A., Ferrua, C., Mitra, R., Phipps, T., Wahl, L. A., Lane, H. C., Fauci, A. S., & Burke, D. S. (1988). Efficient isolation and propagation of human immunodeficiency virus on recombinant colony‐stimulating factor 1‐treated monocytes. Journal of Experimental Medicine, 167, 1428–1441.
Giannarelli, C., Klein, R. S., & Badimon, J. J. (2011). Cardiovascular implications of HIV‐induced dyslipidemia. Atherosclerosis, 219, 384–389.
Giese, S. I., Woerz, I., Homann, S., Tibroni, N., Geyer, M., & Fackler, O. T. (2006). Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV‐1(SF2) Nef. Virology, 355, 175–191.
Gorgens, A., Corso, G., Hagey, D. W., Jawad Wiklander, R., Gustafsson, M. O., Felldin, U., Lee, Y., Bostancioglu, R. B., Sork, H., Liang, X., Zheng, W., Mohammad, D. K., van de Wakker, S. I., Vader, P., Zickler, A. M., Mamand, D. R., Ma, L., Holme, M. N., Stevens, M. M., … El Andaloussi, S. (2022). Identification of storage conditions stabilizing extracellular vesicles preparations. Journal of Extracellular Vesicles, 11, e12238.
Groot Kormelink, T., Mol, S., de Jong, E. C., & Wauben, M. H. M. (2018). The role of extracellular vesicles when innate meets adaptive. Seminars in Immunopathology, 40, 439–452.
Hunegnaw, R., Vassylyeva, M., Dubrovsky, L., Pushkarsky, T., Sviridov, D., Anashkina, A. A., Uren, A., Brichacek, B., Vassylyev, D., Adzhubei, A. A., & Bukrinsky, M. (2016). Interaction between HIV‐1 Nef and calnexin: From modeling to small molecule inhibitors reversing HIV‐induced lipid accumulation. Arteriosclerosis, Thrombosis, and Vascular Biology, 36, 1758–1771.
Johnsen, K. B., Gudbergsson, J. M., Andresen, T. L., & Simonsen, J. B. (2019). What is the blood concentration of extracellular vesicles? Implications for the use of extracellular vesicles as blood‐borne biomarkers of cancer. Biochimica et Biophysica Acta Reviews on Cancer, 1871, 109–116.
Juhl, A. D., & Wustner, D. (2022). Pathways and mechanisms of cellular cholesterol efflux‐insight from imaging. Frontiers in Cell and Developmental Biology, 10, 834408.
Kotov, A., Zhou, J., Flicker, P., & Aiken, C. (1999). Association of Nef with the human immunodeficiency virus type 1 core. Journal of Virology, 73, 8824–8830.
Kowal, J., Arras, G., Colombo, M., Jouve, M., Morath, J. P., Primdal‐Bengtson, B., Dingli, F., Loew, D., Tkach, M., & Thery, C. (2016). Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. PNAS, 113, tE968‐EE77.
Lee, J. H., Schierer, S., Blume, K., Dindorf, J., Wittki, S., Xiang, W., Ostalecki, C., Koliha, N., Wild, S., Schuler, G., Fackler, O. T., Saksela, K., Harrer, T., & Baur, A. S. (2016). HIV‐Nef and ADAM17‐containing plasma extracellular vesicles induce and correlate with immune pathogenesis in chronic HIV infection. EBioMed, 6, 103–113.
Lenassi, M., Cagney, G., Liao, M., Vaupotic, T., Bartholomeeusen, K., Cheng, Y., Krogan, N. J., Plemenitas, A., & Peterlin, B. M. (2010). HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic (Copenhagen, Denmark), 11, 110–122.
Lin, S., Nadeau, P. E., Wang, X., & Mergia, A. (2012). Caveolin‐1 reduces HIV‐1 infectivity by restoration of HIV Nef mediated impairment of cholesterol efflux by apoA‐I. Retrovirology, 9, 85.
Livshits, M. A., Khomyakova, E., Evtushenko, E. G., Lazarev, V. N., Kulemin, N. A., Semina, S. E., Generozov, E. V., & Govorun, V. M. (2015). Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol. Scientific Reports, 5, 17319.
Luo, X., Fan, Y., Park, I. W., & He, J. J. (2015). Exosomes are unlikely involved in intercellular Nef transfer. PLoS ONE, 10, e0124436.
Margolis, L. (2015). Immunoactivation at the crossroads of human disease. American Journal of Medicine, 128, 562–566.
Martin‐Jaular, L., Nevo, N., Schessner, J. P., Tkach, M., Jouve, M., Dingli, F., Loew, D., Witwer, K. W., Ostrowski, M., Borner, G. H. H., & Thery, C. (2021). Unbiased proteomic profiling of host cell extracellular vesicle composition and dynamics upon HIV‐1 infection. Embo Journal, 40, e105492.
Mastronarde, D. N. (2005). Automated electron microscope tomography using robust prediction of specimen movements. Journal of Structural Biology, 152, 36–51.
Matthies, D., Lee, N. Y. J., Gatera, I., Pasolli, H. A., Zhao, X., Liu, H., Walpita, D., Liu, Z., Yu, Z., & Ioannou, M. S. (2020). Microdomains form on the luminal face of neuronal extracellular vesicle membranes. Scientific Reports, 10, 11953.
McNamara, R. P., Costantini, L. M., Myers, T. A., Schouest, B., Maness, N. J., Griffith, J. D., Damania, B. A., & MacLean, A. G. (2018). Dittmer DP. Nef secretion into extracellular vesicles or exosomes is conserved across Human and Simian Immunodeficiency Viruses. MBio, 9, e02344‐e02317.
Mercurio, V., Fitzgerald, W., Vanpouille, C., Molodtsov, I., & Margolis, L. (2021). Mechanisms of residual immune activation in HIV‐1‐infected human lymphoid tissue ex vivo. Aids, 35, 1179–1190.
Mujawar, Z., Rose, H., Morrow, M. P., Pushkarsky, T., Dubrovsky, L., Mukhamedova, N., Fu, Y., Dart, A., Orenstein, J. M., Bobryshev, Y. V., Bukrinsky, M., & Sviridov, D. (2006). Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biology, 4, e365.
Mukhamedova, N., Hoang, A., Dragoljevic, D., Dubrovsky, L., Pushkarsky, T., Low, H., Ditiatkovski, M., Fu, Y., Ohkawa, R., Meikle, P. J., Horvath, A., Brichacek, B., Miller, Y. I., Murphy, A., Bukrinsky, M., & Sviridov, D. (2019). Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells. Plos Pathogens, 15, e1007907.
Nolte‐’t Hoen, E., Cremer, T., Gallo, R. C., & Margolis, L. B. (2016). Extracellular vesicles and viruses: Are they close relatives? PNAS, 113, 9155–9161.
Norman, M., Ter‐Ovanesyan, D., Trieu, W., Lazarovits, R., Kowal, E. J. K., Lee, J. H., Chen‐Plotkin, A. S., Regev, A., Church, G. M., & Walt, D. R. (2021). L1CAM is not associated with extracellular vesicles in human cerebrospinal fluid or plasma. Nature Methods, 18, 631–634.
Odorizzi, G. (2006). The multiple personalities of Alix. Journal of Cell Science, 119, 3025–3032.
Pandori, M. W., Fitch, N. J., Craig, H. M., Richman, D. D., Spina, C. A., & Guatelli, J. C. (1996). Producer‐cell modification of human immunodeficiency virus type 1: Nef is a virion protein. Journal of Virology, 70, 4283–4290.
Pegtel, D. M., & Gould, S. J. (2019). Exosomes. Annual Review of Biochemistry, 88, 487–514.
Peters, B., Post, F., Wierzbicki, A. S., Phillips, A., Power, L., Das, S., Johnson, M., Moyle, G., Hughes, L., Wilkins, E., McCloskey, E., Compston, J., & Di Angelantonio, E. (2013). Screening for chronic comorbid diseases in people with HIV: The need for a strategic approach. HIV Medicine, 14(Suppl 1), 1–11.
Pushkarsky, T., Ward, A., Ivanov, A., Lin, X., Sviridov, D., Nekhai, S., & Bukrinsky, M. I. (2022). Abundance of Nef and p‐Tau217 in brains of individuals diagnosed with HIV‐associated neurocognitive disorders correlate with disease severance. Molecular Neurobiology, 59, 1088–1097.
Raymond, A. D., Campbell‐Sims, T. C., Khan, M., Lang, M., Huang, M. B., Bond, V. C., & Powell, M. D. (2011). HIV Type 1 Nef is released from infected cells in CD45(+) microvesicles and is present in the plasma of HIV‐infected individuals. Aids Research and Human Retroviruses, 27, 167–178.
Remaley, A. T., Stonik, J. A., Demosky, S. J., Neufeld, E. B., Bocharov, A. V., Vishnyakova, T. G., Eggerman, T. L., Patterson, A. P., Duverger, N. J., Santamarina‐Fojo, S., & Brewer, H. B., Jr. (2001). Apolipoprotein specificity for lipid efflux by the human ABCAI transporter. Biochemical and Biophysical Research Communications, 280, 818–823.
Remaley, A. T., Thomas, F., Stonik, J. A., Demosky, S. J., Bark, S. E., Neufeld, E. B., Bocharov, A. V., Vishnyakova, T. G., Patterson, A. P., Eggerman, T. L., Santamarina‐Fojo, S., & Brewer, H. B. (2003). Synthetic amphipathic helical peptides promote lipid efflux from cells by an ABCA1‐dependent and an ABCA1‐independent pathway. Journal of Lipid Research, 44, 828–836.
Rezaie, J., Aslan, C., Ahmadi, M., Zolbanin, N. M., Kashanchi, F., & Jafari, R. (2021). The versatile role of exosomes in human retroviral infections: From immunopathogenesis to clinical application. Cell & Bioscience, 11, 19.
Rider, M. A., Hurwitz, S. N., & Meckes, D. G., Jr (2016). ExtraPEG: A polyethylene glycol‐based method for enrichment of extracellular vesicles. Scientific Reports, 6, 23978.
Sawai, E. T., Baur, A. S., Peterlin, B. M., Levy, J. A., & Cheng‐Mayer, C. (1995). A conserved domain and membrane targeting of Nef from HIV and SIV are required for association with a cellular serine kinase activity. Journal of Biological Chemistry, 270, 15307–15314.
Schmidtmayerova, H., Nuovo, G. J., & Bukrinsky, M. (1997). Cell proliferation is not required for productive HIV‐1 infection of macrophages. Virology, 232, 379–384.
Schwab, A., Meyering, S. S., Lepene, B., Iordanskiy, S., van Hoek, M. L., Hakami, R. M., & Kashanchi, F. (2015). Extracellular vesicles from infected cells: Potential for direct pathogenesis. Frontiers in Microbiology, 6, 1132.
Siegel, J., Darwish, C., Popratiloff, A., Bukrinsky, M., & Brichacek, B. (2016). Live cell imaging of ABCA1 downregulation by HIV‐1 Nef in an experimental model of HeLa ABCA1‐GFP. Aids Research and Human Retroviruses, 32, 872–873.
Singh, P., Yadav, G. P., Gupta, S., Tripathi, A. K., Ramachandran, R., & Tripathi, R. K. (2011). A novel dimer‐tetramer transition captured by the crystal structure of the HIV‐1 Nef. PLoS ONE, 6, e26629.
Stevenson, E. M., Ward, A. R., Truong, R., Thomas, A. S., Huang, S. H., Dilling, T. R., Terry, S., Bui, J. K., Mota, T. M., Danesh, A., Lee, G. Q., Gramatica, A., Khadka, P., Alberto, W. D. C., Gandhi, R. T., McMahon, D. K., Lalama, C. M., Bosch, R. J., Macatangay, B., … Jones, R. B. (2021). Team ACTGA. HIV‐specific T cell responses reflect substantive in vivo interactions with antigen despite long‐term therapy. JCI Insight, 6, e142640.
Sviridov, D., Mukhamedova, N., Makarov, A. A., Adzhubei, A., & Bukrinsky, M. (2020). Comorbidities of HIV infection: Role of Nef‐induced impairment of cholesterol metabolism and lipid raft functionality. Aids, 34, 1–13.
Triant, V. A., Perez, J., Regan, S., Massaro, J. M., Meigs, J. B., Grinspoon, S. K., & D'Agostino Sr, R. B. (2018). Cardiovascular risk prediction functions underestimate risk in HIV infection. Circulation, 137, 2203–2214.
Vanpouille, C., Introini, A., Morris, S. R., Margolis, L., Daar, E. S., Dube, M. P., Little, S. J., Smith, D. M., Lisco, A., & Gianella, S. (2016). Distinct cytokine/chemokine network in semen and blood characterize different stages of HIV infection. Aids, 30, 193–201.
Welker, R., Harris, M., Cardel, B., & Krausslich, H. G. (1998). Virion incorporation of human immunodeficiency virus type 1 Nef is mediated by a bipartite membrane‐targeting signal: Analysis of its role in enhancement of viral infectivity. Journal of Virology, 72, 8833–8840.
Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrugger, U., Falcon‐Perez, J. M., Fu, Q. L., Hill, A. F., Lenassi, M., Lim, S. K., Mahoney, M. G., Mohanty, S., Moller, A., Nieuwland, R., … Witwer, K. W. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. Journal of Extracellular Vesicles, 13, e12404.
Wu, V. H., Nordin, J. M. L., Nguyen, S., Joy, J., Mampe, F., Del Rio Estrada, P. M., Torres‐Ruiz, F., Gonzalez‐Navarro, M., Luna‐Villalobos, Y. A., Avila‐Rios, S., Reyes‐Teran, G., Tebas, P., Montaner, L. J., Bar, K. J., Vella, L. A., & Betts, M. R. (2023). Profound phenotypic and epigenetic heterogeneity of the HIV‐1‐infected CD4(+) T cell reservoir. Nature Immunology, 24, 359–370.
Zicari, S., Sessa, L., Cotugno, N., Ruggiero, A., Morrocchi, E., Concato, C., Rocca, S., Zangari, P., Manno, E. C., & Palma, P. (2019). Immune Activation, Inflammation, and Non‐AIDS Co‐Morbidities in HIV‐Infected Patients under Long‐Term ART. Viruses., 11, 200.

Auteurs

Christophe Vanpouille (C)

Section on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Beda Brichacek (B)

Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

Tatiana Pushkarsky (T)

Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

Larisa Dubrovsky (L)

Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

Wendy Fitzgerald (W)

Section on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Nigora Mukhamedova (N)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Sofia Garcia-Hernandez (S)

Nanofabrication and Imaging Center, The George Washington University, Washington, District of Columbia, USA.

Doreen Matthies (D)

Unit on Structural Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Anastas Popratiloff (A)

Nanofabrication and Imaging Center, The George Washington University, Washington, District of Columbia, USA.

Dmitri Sviridov (D)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.

Leonid Margolis (L)

Section on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, Republic of Georgia.

Michael Bukrinsky (M)

Department of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

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