Satish Pillai, PhD

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Satish Pillai, PhD

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Senior Investigator, Viral Pathogenesis, Vitalant Research Institute
Professor, School of Medicine
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Biography

My laboratory uses a systems biology approach to decipher the antiretroviral effects of IFN-α in vivo, by studying host gene expression, viral production and viral evolution in HIV-1-infected individuals undergoing IFN-α therapy. Recent data generated by our group strongly suggest that IFN-α suppresses HIV-1 replication in chronically-infected individuals by inducing intrinsic cellular inhibitors of retroviral replication known as host restriction factors. One of these factors, the cytidine deaminase APOBEC3G, blocks HIV-1 infection by hyper-mutating the viral genome such that it no longer encodes functional proteins that are necessary for viral replication. Another factor, the type 2 integral membrane protein BST-2/tetherin, blocks HIV-1 infection by restricting the release of fully formed progeny virions from infected cells. Our data warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

In addition to my principal research projects involving IFN-α and cell-intrinsic immunity, I participate as a bioinformaticist and phylogeneticist in a number of HIV/AIDS collaborations with researchers at the San Francisco VA Medical Center (SFVAMC), San Francisco General Hospital (SFGH) and the Gladstone Institute of Virology and Immunology (GIVI).

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  1. Abdel-Mohsen M, Deng X, Liegler T, Guatelli JC, Salama MS, Ghanem Hel-D, Rauch A, Ledergerber B, Deeks SG, Günthard HF, Wong JK, Pillai SK. Effects of alpha interferon treatment on intrinsic anti-HIV-1 immunity in vivo. J Virol. 2014 Jan; 88(1):763-7.
  2. Abdel-Mohsen M, Raposo RA, Deng X, Li M, Liegler T, Sinclair E, Salama MS, Ghanem Hel-D, Hoh R, Wong JK, David M, Nixon DF, Deeks SG, Pillai SK. Expression profile of host restriction factors in HIV-1 elite controllers. Retrovirology. 2013 Oct 16; 10:106.
  3. Rempel H, Sun B, Calosing C, Pillai SK, Pulliam L. Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection. AIDS. 2010 Jun 19; 24(10):1415-23.
  4. Raposo RA, Abdel-Mohsen M, Bilska M, Montefiori DC, Nixon DF, Pillai SK. Effects of cellular activation on anti-HIV-1 restriction factor expression profile in primary cells. J Virol. 2013 Nov; 87(21):11924-9.
  5. Raposo RA, Abdel-Mohsen M, Holditch SJ, Kuebler PJ, Cheng RG, Eriksson EM, Liao W, Pillai SK, Nixon DF. Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals. J Leukoc Biol. 2013 Nov; 94(5):1051-9.
  6. Yukl SA, Boritz E, Busch M, Bentsen C, Chun TW, Douek D, Eisele E, Haase A, Ho YC, Hütter G, Justement JS, Keating S, Lee TH, Li P, Murray D, Palmer S, Pilcher C, Pillai S, Price RW, Rothenberger M, Schacker T, Siliciano J, Siliciano R, Sinclair E, Strain M, Wong J, Richman D, Deeks SG. Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog. 2013; 9(5):e1003347.
  7. Pillai SK, Abdel-Mohsen M, Guatelli J, Skasko M, Monto A, Fujimoto K, Yukl S, Greene WC, Kovari H, Rauch A, Fellay J, Battegay M, Hirschel B, Witteck A, Bernasconi E, Ledergerber B, Günthard HF, Wong JK, Swiss HIV Cohort Study . Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):3035-40.
  8. Yukl S, Pillai S, Li P, Chang K, Pasutti W, Ahlgren C, Havlir D, Strain M, Günthard H, Richman D, Rice AP, Daar E, Little S, Wong JK. Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity. Virology. 2009 Apr 25; 387(1):98-108.
  9. Skasko M, Tokarev A, Chen CC, Fischer WB, Pillai SK, Guatelli J. BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Virology. 2011 Mar 01; 411(1):65-77.
  10. Rempel H, Sun B, Calosing C, Pillai SK, Pulliam L. Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection. AIDS. 2010 Jun 19; 24(10):1415-23.
  11. Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, Ignacio CC, Russell T, Pillai SK, Looney DJ, Dandekar S. In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells. PLoS Pathog. 2010 Jan 29; 6(1):e1000748.
  12. Manosuthi W, Butler DM, Pérez-Santiago J, Poon AF, Pillai SK, Mehta SR, Pacold ME, Richman DD, Pond SK, Smith DM. Protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure. AIDS. 2010 Jan 28; 24(3):411-6.
  13. Jha AR, Pillai SK, York VA, Sharp ER, Storm EC, Wachter DJ, Martin JN, Deeks SG, Rosenberg MG, Nixon DF, Garrison KE. Cross-sectional dating of novel haplotypes of HERV-K 113 and HERV-K 115 indicate these proviruses originated in Africa before Homo sapiens. Mol Biol Evol. 2009 Nov; 26(11):2617-26.
  14. Joos B, Rieder P, Fischer M, Kuster H, Rusert P, Trkola A, Pillai SK, Wong JK, Weber R, Günthard HF. Association between specific HIV-1 Env traits and virologic control in vivo. Infect Genet Evol. 2010 Apr; 10(3):365-72.
  15. Yukl S, Pillai S, Li P, Chang K, Pasutti W, Ahlgren C, Havlir D, Strain M, Günthard H, Richman D, Rice AP, Daar E, Little S, Wong JK. Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity. Virology. 2009 Apr 25; 387(1):98-108.
  16. Smith DM, Zárate S, Shao H, Pillai SK, Letendre SL, Wong JK, Richman DD, Frost SD, Ellis RJ, HNRC Group . Pleocytosis is associated with disruption of HIV compartmentalization between blood and cerebral spinal fluid viral populations. Virology. 2009 Mar 01; 385(1):204-8.
  17. Joos B, Fischer M, Kuster H, Pillai SK, Wong JK, Böni J, Hirschel B, Weber R, Trkola A, Günthard HF, Swiss HIV Cohort Study . HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci U S A. 2008 Oct 28; 105(43):16725-30.
  18. Kosakovsky Pond SL, Poon AF, Zárate S, Smith DM, Little SJ, Pillai SK, Ellis RJ, Wong JK, Leigh Brown AJ, Richman DD, Frost SD. Estimating selection pressures on HIV-1 using phylogenetic likelihood models. Stat Med. 2008 Oct 15; 27(23):4779-89.
  19. Pilcher CD, Wong JK, Pillai SK. Inferring HIV transmission dynamics from phylogenetic sequence relationships. PLoS Med. 2008 Mar 18; 5(3):e69.
  20. Pillai SK, Wong JK, Barbour JD. Turning up the volume on mutational pressure: is more of a good thing always better? (A case study of HIV-1 Vif and APOBEC3). Retrovirology. 2008 Mar 13; 5:26.
  21. Low AJ, Dong W, Chan D, Sing T, Swanstrom R, Jensen M, Pillai S, Good B, Harrigan PR. Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates. AIDS. 2007 Sep 12; 21(14):F17-24.
  22. Willberg CB, Pillai SK, Sharp ER, Rosenberg MG, Agudelo JD, Barbour JD, Nixon DF. Rational peptide selection to detect human immunodeficiency virus type 1-specific T-cell responses under resource-limited conditions. Clin Vaccine Immunol. 2007 Jun; 14(6):785-8.
  23. Noviello CM, Pond SL, Lewis MJ, Richman DD, Pillai SK, Yang OO, Little SJ, Smith DM, Guatelli JC. Maintenance of Nef-mediated modulation of major histocompatibility complex class I and CD4 after sexual transmission of human immunodeficiency virus type 1. J Virol. 2007 May; 81(9):4776-86.
  24. Smith DM, Strain MC, Frost SD, Pillai SK, Wong JK, Wrin T, Liu Y, Petropolous CJ, Daar ES, Little SJ, Richman DD. Lack of neutralizing antibody response to HIV-1 predisposes to superinfection. Virology. 2006 Nov 10; 355(1):1-5.
  25. Pillai SK, Pond SL, Liu Y, Good BM, Strain MC, Ellis RJ, Letendre S, Smith DM, Günthard HF, Grant I, Marcotte TD, McCutchan JA, Richman DD, Wong JK. Genetic attributes of cerebrospinal fluid-derived HIV-1 env. Brain. 2006 Jul; 129(Pt 7):1872-83.