Our laboratory studies the interplay between the innate and adaptive immune response against retroviruses to conceptually advance vaccine and cure strategies against HIV/AIDS and SARS-CoV-2. We are specifically interested in “restriction factors” – host proteins that could directly inhibit viruses but we discovered also play critical roles in shaping adaptive immune responses. These factors could be regulated by Type I interferons, thus highlighting possibilities for clinical translation.
Publications
Olson D, Calvimontes DM, Lamb MM, Guzman G, Barrios E, Chacon A, Rojop N, Arias K, Gomez M, Bolanos GA, Monzon J, Chard AN, Iwamoto C, Duca LM, Vuong N, Fineman M, Lesteberg K, Beckham D, Santiago ML, Quicke K, Ebel G, Gutierrez EZ, Azziz-Baumgartner E, Hayden FG, Mansour H, Edwards K, Newman LS, Asturias EJ. Clinical and Economic Impact of COVID-19 on Agricultural Workers, Guatemala(1). Emerg Infect Dis. 2022 Dec;28(13):S277-S287. PubMed PMID: 36502430
Jones ST, Guo K, Cooper EH, Dillon SM, Wood C, Nguyen DH, Shen G, Barrett BS, Frank DN, Kroehl M, Janoff EN, Kechris K, Wilson CC, Santiago ML. Altered Immunoglobulin Repertoire and Decreased IgA Somatic Hypermutation in the Gut during Chronic HIV-1 Infection. J Virol. 2022 Sep 14;96(17):e0097622. PubMed PMID: 35938870
Iwamoto C, Lesteberg KE, Lamb MM, Calvimontes DM, Guo K, Barrett BS, Mickens KL, Duca LM, Monzon J, Chard AN, Guzman G, Barrios E, Rojop N, Arias K, Gomez M, Paiz C, Bolanos GA, Edwards KM, Zielinski Gutierrez E, Azziz-Baumgartner E, Asturias EJ, Santiago ML, Beckham JD, Olson D. High SARS-CoV-2 Seroprevalence and Rapid Neutralizing Antibody Decline among Agricultural Workers in Rural Guatemala, June 2020-March 2021. Vaccines (Basel). 2022 Jul 21;10(7). PubMed PMID: 35891324
Guo K, Barrett BS, Morrison JH, Mickens KL, Vladar EK, Hasenkrug KJ, Poeschla EM, Santiago ML. Interferon resistance of emerging SARS-CoV-2 variants. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2203760119. PubMed PMID: 35867811
Warren CJ, Santiago ML, Pyeon D. APOBEC3: Friend or Foe in Human Papillomavirus Infection and Oncogenesis?. Annu Rev Virol. 2022 Sep 29;9(1):375-395. PubMed PMID: 35671565
Dillon SM, Mickens KL, Thompson TA, Cooper EH, Nesladek S, Christians AJ, Castleman M, Guo K, Wood C, Frank DN, Kechris K, Santiago ML, Wilson CC. Granzyme B( ) CD4 T cells accumulate in the colon during chronic HIV-1 infection. Gut Microbes. 2022 Jan-Dec;14(1):2045852. PubMed PMID: 35258402
Galbraith MD, Kinning KT, Sullivan KD, Araya P, Smith KP, Granrath RE, Shaw JR, Baxter R, Jordan KR, Russell S, Dzieciatkowska M, Reisz JA, Gamboni F, Cendali F, Ghosh T, Guo K, Wilson CC, Santiago ML, Monte AA, Bennett TD, Hansen KC, Hsieh EWY, D'Alessandro A, Espinosa JM. Specialized interferon action in COVID-19. Proc Natl Acad Sci U S A. 2022 Mar 15;119(11). PubMed PMID: 35217532
Windsor WJ, Knight V, Merkel PA, Lamb MM, Tucker HR, Carson K, Howard KM, Yates JL, Santiago ML, McCarthy MK, Morrison TE, Kedl RM, Frazer-Abel A, Guo K, Andersen G, Huey L, Barrett BS, Colón-Franco JM, Lee WT, Chu MC. COVID-19 Serology Control Panel Using the Dried-Tube Specimen Method. Am J Trop Med Hyg. 2022 Jan 7;106(2):562-565. PubMed PMID: 34996045
Sertznig H, Roesmann F, Wilhelm A, Heininger D, Bleekmann B, Elsner C, Santiago M, Schuhenn J, Karakoese Z, Benatzy Y, Snodgrass R, Esser S, Sutter K, Dittmer U, Widera M. SRSF1 acts as an IFN-I-regulated cellular dependency factor decisively affecting HIV-1 post-integration steps. Front Immunol. 2022;13:935800. PubMed PMID: 36458014
Barrett B, Nguyen DH, Xu J, Guo K, Shetty S, Jones ST, Mickens KL, Shepard C, Roers A, Behrendt R, Wu L, Kim B, Santiago ML. SAMHD1 Promotes the Antiretroviral Adaptive Immune Response in Mice Exposed to Lipopolysaccharide. J Immunol. 2022 Jan 15;208(2):444-453. PubMed PMID: 34893529
Hasenkrug KJ, Feldmann F, Myers L, Santiago ML, Guo K, Barrett BS, Mickens KL, Carmody A, Okumura A, Rao D, Collins MM, Messer RJ, Lovaglio J, Shaia C, Rosenke R, van Doremalen N, Clancy C, Saturday G, Hanley P, Smith BJ, Meade-White K, Shupert WL, Hawman DW, Feldmann H. Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques. mBio. 2021 Aug 31;12(4):e0150321. PubMed PMID: 34311582
Castleman MJ, Dillon SM, Thompson TA, Santiago ML, McCarter MD, Barker E, Wilson CC. Gut Bacteria Induce Granzyme B Expression in Human Colonic ILC3s In Vitro in an IL-15-Dependent Manner. J Immunol. 2021 Jun 15;206(12):3043-3052. PubMed PMID: 34117105
Guo K, Barrett BS, Mickens KL, Vladar EK, Morrison JH, Hasenkrug KJ, Poeschla EM, Santiago ML. Interferon Resistance of Emerging SARS-CoV-2 Variants. bioRxiv. 2021 Dec 10. PubMed PMID: 33758840
Guo K, Shen G, Kibbie J, Gonzalez T, Dillon SM, Smith HA, Cooper EH, Lavender K, Hasenkrug KJ, Sutter K, Dittmer U, Kroehl M, Kechris K, Wilson CC, Santiago ML. Qualitative Differences Between the IFNa subtypes and IFNß Influence Chronic Mucosal HIV-1 Pathogenesis. PLoS Pathog. 2020 Oct;16(10):e1008986. PubMed PMID: 33064743
Ickler J, Francois S, Widera M, Santiago ML, Dittmer U, Sutter K. HIV infection does not alter interferon a/ß receptor 2 expression on mucosal immune cells. PLoS One. 2020;15(1):e0218905. PubMed PMID: 31935222
Miller CM, Barrett BS, Chen J, Morrison JH, Radomile C, Santiago ML, Poeschla EM. Systemic Expression of a Viral RdRP Protects against Retrovirus Infection and Disease. J Virol. 2020 Apr 16;94(9). PubMed PMID: 32051266
Agazio A, Cimons J, Shotts KM, Guo K, Santiago ML, Pelanda R, Torres RM. Histone H2A-Reactive B Cells Are Functionally Anergic in Healthy Mice With Potential to Provide Humoral Protection Against HIV-1. Front Immunol. 2020;11:1565. PubMed PMID: 32849530
Dillon SM, Guo K, Castleman MJ, Santiago ML and Wilson CC. Quantifying HIV-1-Mediated Gut CD4+ T cell death in the Lamina Propria Aggregate Culture (LPAC) Model. Bio-Protocol. 2020;10(2):e3486.
Uchil PD, Pi R, Haugh KA, Ladinsky MS, Ventura JD, Barrett BS, Santiago ML, Bjorkman PJ, Kassiotis G, Sewald X, Mothes W. A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. Cell Host Microbe. 2019 Jan 9;25(1):87-100.e10. PubMed PMID: 30595553
Castleman MJ, Dillon SM, Purba CM, Cogswell AC, Kibbie JJ, McCarter MD, Santiago ML, Barker E, Wilson CC. Commensal and Pathogenic Bacteria Indirectly Induce IL-22 but Not IFN? Production From Human Colonic ILC3s via Multiple Mechanisms. Front Immunol. 2019;10:649. PubMed PMID: 30984202
Dittmer U, Sutter K, Kassiotis G, Zelinskyy G, Bánki Z, Stoiber H, Santiago ML, Hasenkrug KJ. Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity. FEMS Microbiol Rev. 2019 Sep 1;43(5):435-456. PubMed PMID: 31087035
Hasenkrug KJ, Lavender KJ, Santiago ML, Sutter K, Dittmer U. Different Biological Activities of Specific Interferon Alpha Subtypes. mSphere. 2019 Jul 24;4(4). PubMed PMID: 31341068
Dickow J, Francois S, Kaiserling RL, Malyshkina A, Drexler I, Westendorf AM, Lang KS, Santiago ML, Dittmer U, Sutter K. Diverse Immunomodulatory Effects of Individual IFNa Subtypes on Virus-Specific CD8( ) T Cell Responses. Front Immunol. 2019;10:2255. PubMed PMID: 31608062
Miller SM, Miles B, Guo K, Folkvord J, Meditz AL, McCarter MD, Levy DN, MaWhinney S, Santiago ML, Connick E. Follicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1. J Virol. 2017 Sep 1;91(17). PubMed PMID: 28615202
Getahun A, Wemlinger SM, Rudra P, Santiago ML, van Dyk LF, Cambier JC. Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway. J Exp Med. 2017 Apr 3;214(4):931-941. PubMed PMID: 28341640
Dillon SM, Kibbie J, Lee EJ, Guo K, Santiago ML, Austin GL, Gianella S, Landay AL, Donovan AM, Frank DN, McCARTER MD, Wilson CC. Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation. AIDS. 2017 Feb 20;31(4):511-521. PubMed PMID: 28002063
Wang Y, Schmitt K, Guo K, Santiago ML, Stephens EB. Role of the single deaminase domain APOBEC3A in virus restriction, retrotransposition, DNA damage and cancer. J Gen Virol. 2016 Jan;97(1):1-17. PubMed PMID: 26489798
Dillon SM, Lee EJ, Donovan AM, Guo K, Harper MS, Frank DN, McCarter MD, Santiago ML, Wilson CC. Enhancement of HIV-1 infection and intestinal CD4 T cell depletion ex vivo by gut microbes altered during chronic HIV-1 infection. Retrovirology. 2016 Jan 14;13:5. PubMed PMID: 26762145
Li SX, Barrett BS, Guo K, Kassiotis G, Hasenkrug KJ, Dittmer U, Gibbert K, Santiago ML. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection. Sci Rep. 2016 Feb 5;6:20425. PubMed PMID: 26846717
Li SX, Barrett BS, Guo K, Santiago ML. Tetherin/BST-2: Restriction Factor or Immunomodulator?. Curr HIV Res. 2016;14(3):235-46. PubMed PMID: 26957198
Lavender KJ, Gibbert K, Peterson KE, Van Dis E, Francois S, Woods T, Messer RJ, Gawanbacht A, Müller JA, Münch J, Phillips K, Race B, Harper MS, Guo K, Lee EJ, Trilling M, Hengel H, Piehler J, Verheyen J, Wilson CC, Santiago ML, Hasenkrug KJ, Dittmer U. Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo. J Virol. 2016 Jul 1;90(13):6001-13. PubMed PMID: 27099312
Wang Y, Wang Z, Pramanik A, Santiago ML, Qiu J, Stephens EB. A chimeric human APOBEC3A protein with a three amino acid insertion confers differential HIV-1 and adeno-associated virus restriction. Virology. 2016 Nov;498:149-63. PubMed PMID: 27584592
Rubtsova K, Rubtsov AV, Halemano K, Li SX, Kappler JW, Santiago ML, Marrack P. T Cell Production of IFN? in Response to TLR7/IL-12 Stimulates Optimal B Cell Responses to Viruses. PLoS One. 2016 Nov 23;11(11):e0166322. PubMed PMID: 27880772
Dillon SM, Kibbie J, Lee EJ, Guo K, Santiago ML, Austin GL, Gianella S, Landay AL, Donovan AM, Frank DN, McCarter MD, Wilson CC. Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation. AIDS. 2016 Dec 19. [Epub ahead of print] PubMed PMID: 28002063
Warren CJ, Xu T, Guo K, Griffin LM, Westrich JA, Lee D, Lambert PF, Santiago ML, Pyeon D. APOBEC3A functions as a restriction factor of human papillomavirus. J Virol. 2015 Jan;89(1):688-702. PubMed PMID: 25355878
Halemano K, Barrett BS, Heilman KJ, Morrison TE, Santiago ML. Requirement for Fc effector mechanisms in the APOBEC3/Rfv3-dependent neutralizing antibody response. J Virol. 2015 Apr;89(7):4011-4. PubMed PMID: 25589647
Guo K, Halemano K, Schmitt K, Katuwal M, Wang Y, Harper MS, Heilman KJ, Kuwata T, Stephens EB, Santiago ML. Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection of rhesus macaques. Immunogenetics. 2015 Jul;67(7):355-70. PubMed PMID: 25994147
Harper MS, Guo K, Gibbert K, Lee EJ, Dillon SM, Barrett BS, McCarter MD, Hasenkrug KJ, Dittmer U, Wilson CC, Santiago ML. Interferon-a Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms. PLoS Pathog. 2015 Nov;11(11):e1005254. PubMed PMID: 26529416
Gibbert K, Francois S, Sigmund AM, Harper MS, Barrett BS, Kirchning CJ, Lu M, Santiago ML, Dittmer U. Friend retrovirus drives cytotoxic effectors through Toll-like receptor 3. Retrovirology. 2014 Dec 24;11(1):1. [Epub ahead of print] PubMed PMID: 25539593
Connick E, Folkvord JM, Lind KT, Rakasz EG, Miles B, Wilson NA, Santiago ML, Schmitt K, Stephens EB, Kim HO, Wagstaff R, Li S, Abdelaal HM, Kemp N, Watkins DI, MaWhinney S, Skinner PJ. Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL. J Immunol. 2014 Dec 1;193(11):5613-25. PubMed PMID: 25362178
Barrett BS, Guo K, Harper MS, Li SX, Heilman KJ, Davidson NO, Santiago ML. Reassessment of murine APOBEC1 as a retrovirus restriction factor in vivo. Virology. 2014 Nov;468-470:601-8. PubMed PMID: 25303118
Katuwal M, Wang Y, Schmitt K, Guo K, Halemano K, Santiago ML, Stephens EB. Cellular HIV-1 inhibition by truncated old world primate APOBEC3A proteins lacking a complete deaminase domain. Virology. 2014 Nov;468-470:532-44. PubMed PMID: 25262471
Li SX, Barrett BS, Heilman KJ, Messer RJ, Liberatore RA, Bieniasz PD, Kassiotis G, Hasenkrug KJ, Santiago ML. Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo. J Immunol. 2014 Jul 1;193(1):306-16. PubMed PMID: 24872193
Halemano K, Guo K, Heilman KJ, Barrett BS, Smith DS, Hasenkrug KJ, Santiago ML. Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection. Proc Natl Acad Sci U S A. 2014 May 27;111(21):7759-64. PubMed PMID: 24821801
Steele AK, Lee EJ, Manuzak JA, Dillon SM, Beckham JD, McCarter MD, Santiago ML, Wilson CC. Microbial exposure alters HIV-1-induced mucosal CD4 T cell death pathways Ex vivo. Retrovirology. 2014 Feb 4;11:14. PubMed PMID: 24495380
Cavrois M, Neidleman J, Santiago ML, Derdeyn CA, Hunter E, Greene WC. Enhanced fusion and virion incorporation for HIV-1 subtype C envelope glycoproteins with compact V1/V2 domains. J Virol. 2014 Feb;88(4):2083-94. PubMed PMID: 24335304