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    Satish Pillai, PhD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentLaboratory Medicine
    AddressBlood Systems Research Inst.
    270 Masonic Ave, S.F. CA 94118
    Phone415-513-4461

       Overview 
       Overview
      Despite nearly three decades of focused research since the discovery of HIV-1, to date there is no cure or effective prophylactic vaccine for HIV-1 infection. Although the advent of Highly Active Antiretroviral Therapy (HAART) has dramatically decreased the morbidity and mortality associated with HIV-1 infection, there is a pronounced demand for alternative clinical management strategies due to frequent evolution of antiretroviral resistance, toxicity, and access constraints in resource-limited settings. My research is focused on identifying and characterizing novel host factors that act against HIV-1, by investigating the molecular determinants underlying the anti-HIV-1 activity of the antiviral cytokine interferon-alpha (IFN-a) in vivo. These host factors may serve as the foundations of future prophylactic, therapeutic and eradication strategies for HIV-1 infection.

      Induction of IFN-a expression is a critical first step in the defense against a range of viral infections. The antiretroviral activity of the IFN-a cytokine was demonstrated in vitro almost immediately after the discovery of HIV-1, and includes inhibition of HIV-1 reverse transcription, viral assembly and virion release. Several clinical studies including our own report that IFN-a treatment acts against HIV-1 in vivo, and potently suppresses HIV-1 viremia in chronically-infected individuals. The precise molecular mechanisms underlying this suppressive activity in vivo, however, remain to be elucidated.

      My laboratory uses a systems biology approach to decipher the antiretroviral effects of IFN-a in vivo, by studying host gene expression, viral production and viral evolution in HIV-1-infected individuals undergoing IFN-a therapy. Recent data generated by our group strongly suggest that IFN-a 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 APOBEC3, blocks HIV-1 infection by hypermutating the viral genome so 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. For a concise explanation of my latest research and its implications, please visit this new UCSF press release:

      http://www.ucsf.edu/news/2012/02/11598/fighting-infections-old-drug-reveals-new-tricks

      In addition to the my principal research projects involving IFN-a and host restriction factors, 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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       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Forrester JD, Hunter JC, Pillai SK, Arwady MA, Ayscue P, Matanock A, Monroe B, Schafer IJ, Nyenswah TG, De Cock KM. Cluster of ebola cases among liberian and u.s. Health care workers in an ebola treatment unit and adjacent hospital - liberia, 2014. MMWR Morb Mortal Wkly Rep. 2014 Oct 17; 63(41):925-9.
        View in: PubMed
      2. Pillai SK, Nyenswah T, Rouse E, Arwady MA, Forrester JD, Hunter JC, Matanock A, Ayscue P, Monroe B, Schafer IJ, Poblano L, Neatherlin J, Montgomery JM, De Cock KM. Developing an incident management system to support ebola response - liberia, july-august 2014. MMWR Morb Mortal Wkly Rep. 2014 Oct 17; 63(41):930-3.
        View in: PubMed
      3. Forrester JD, Pillai SK, Beer KD, Neatherlin J, Massaquoi M, Nyenswah TG, Montgomery JM, Cock KD. Assessment of ebola virus disease, health care infrastructure, and preparedness - four counties, southeastern liberia, august 2014. MMWR Morb Mortal Wkly Rep. 2014 Oct 10; 63(40):891-3.
        View in: PubMed
      4. Abdel-Mohsen M, Deng X, Danesh A, Liegler T, Jacobs ES, Rauch A, Ledergerber B, Norris PJ, Günthard HF, Wong JK, Pillai SK. Role of MicroRNA Modulation in the Interferon-a/Ribavirin Suppression of HIV-1 In Vivo. PLoS One. 2014; 9(10):e109220.
        View in: PubMed
      5. Saraiva Raposo RA, Abdel-Mohsen M, Deng X, Hecht FM, Pilcher CD, Pillai SK, Nixon DF. Dynamic regulation of host restriction factor expression over the course of HIV-1 infection in vivo. J Virol. 2014 Jul 16.
        View in: PubMed
      6. Wang C, Abdel-Mohsen M, Strain MC, Lada SM, Yukl S, Cockerham L, Pilcher CD, Hecht FM, Sinclair E, Liegler T, Richman DD, Deeks SG, Pillai SK. Decreased HIV-1 Transcription in CCR5 Delta-32 Heterozygotes On Suppressive Antiretroviral Therapy. J Infect Dis. 2014 Jun 16.
        View in: PubMed
      7. 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.
        View in: PubMed
      8. 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; 10(1):106.
        View in: PubMed
      9. Zou S, Glynn S, Kuritzkes D, Shah M, Cook N, Berliner N. Hematopoietic cell transplantation and HIV cure: where we are and what next? Blood. 2013 Oct 31; 122(18):3111-5.
        View in: PubMed
      10. 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.
        View in: PubMed
      11. 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.
        View in: PubMed
      12. 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.
        View in: PubMed
      13. 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. Role of retroviral restriction factors in the interferon-a-mediated suppression of HIV-1 in vivo. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):3035-40.
        View in: PubMed
      14. Jha AR, Nixon DF, Rosenberg MG, Martin JN, Deeks SG, Hudson RR, Garrison KE, Pillai SK. Human endogenous retrovirus K106 (HERV-K106) was infectious after the emergence of anatomically modern humans. PLoS One. 2011; 6(5):e20234.
        View in: PubMed
      15. 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 1; 411(1):65-77.
        View in: PubMed
      16. 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.
        View in: PubMed
      17. 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; 6(1):e1000748.
        View in: PubMed
      18. 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.
        View in: PubMed
      19. 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.
        View in: PubMed
      20. 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.
        View in: PubMed
      21. 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.
        View in: PubMed
      22. Smith DM, Zárate S, Shao H, Pillai SK, Letendre SL, Wong JK, Richman DD, Frost SD, Ellis RJ. Pleocytosis is associated with disruption of HIV compartmentalization between blood and cerebral spinal fluid viral populations. Virology. 2009 Mar 1; 385(1):204-8.
        View in: PubMed
      23. Joos B, Fischer M, Kuster H, Pillai SK, Wong JK, Böni J, Hirschel B, Weber R, Trkola A, Günthard HF. 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.
        View in: PubMed
      24. 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.
        View in: PubMed
      25. Pilcher CD, Wong JK, Pillai SK. Inferring HIV transmission dynamics from phylogenetic sequence relationships. PLoS Med. 2008 Mar 18; 5(3):e69.
        View in: PubMed
      26. 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; 5:26.
        View in: PubMed
      27. 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.
        View in: PubMed
      28. 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.
        View in: PubMed
      29. 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.
        View in: PubMed
      30. 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.
        View in: PubMed
      31. 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.
        View in: PubMed
      32. Coleman SH, Madrid R, Van Damme N, Mitchell RS, Bouchet J, Servant C, Pillai S, Benichou S, Guatelli JC. Modulation of cellular protein trafficking by human immunodeficiency virus type 1 Nef: role of the acidic residue in the ExxxLL motif. J Virol. 2006 Feb; 80(4):1837-49.
        View in: PubMed
      33. Pillai SK, Kosakovsky Pond SL, Woelk CH, Richman DD, Smith DM. Codon volatility does not reflect selective pressure on the HIV-1 genome. Virology. 2005 Jun 5; 336(2):137-43.
        View in: PubMed
      34. Strain MC, Letendre S, Pillai SK, Russell T, Ignacio CC, Günthard HF, Good B, Smith DM, Wolinsky SM, Furtado M, Marquie-Beck J, Durelle J, Grant I, Richman DD, Marcotte T, McCutchan JA, Ellis RJ, Wong JK. Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy. J Virol. 2005 Feb; 79(3):1772-88.
        View in: PubMed
      35. Pillai SK, Good B, Pond SK, Wong JK, Strain MC, Richman DD, Smith DM. Semen-specific genetic characteristics of human immunodeficiency virus type 1 env. J Virol. 2005 Feb; 79(3):1734-42.
        View in: PubMed
      36. Yu Q, König R, Pillai S, Chiles K, Kearney M, Palmer S, Richman D, Coffin JM, Landau NR. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol. 2004 May; 11(5):435-42.
        View in: PubMed
      37. Kunstman KJ, Puffer B, Korber BT, Kuiken C, Smith UR, Kunstman J, Stanton J, Agy M, Shibata R, Yoder AD, Pillai S, Doms RW, Marx P, Wolinsky SM. Structure and function of CC-chemokine receptor 5 homologues derived from representative primate species and subspecies of the taxonomic suborders Prosimii and Anthropoidea. J Virol. 2003 Nov; 77(22):12310-8.
        View in: PubMed
      38. Ali A, Pillai S, Ng H, Lubong R, Richman DD, Jamieson BD, Ding Y, McElrath MJ, Guatelli JC, Yang OO. Broadly increased sensitivity to cytotoxic T lymphocytes resulting from Nef epitope escape mutations. J Immunol. 2003 Oct 15; 171(8):3999-4005.
        View in: PubMed
      39. Pillai S, Good B, Richman D, Corbeil J. A new perspective on V3 phenotype prediction. AIDS Res Hum Retroviruses. 2003 Feb; 19(2):145-9.
        View in: PubMed
      40. Kalish ML, Korber BT, Pillai S, Robbins KE, Leo YS, Saekhou A, Verghese I, Gerrish P, Goh CL, Lupo D, Tan BH, Brown TM, Chan R. The sequential introduction of HIV-1 subtype B and CRF01AE in Singapore by sexual transmission: accelerated V3 region evolution in a subpopulation of Asian CRF01 viruses. Virology. 2002 Dec 20; 304(2):311-29.
        View in: PubMed
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