AIDS and Cancer Virus Program

Biography

Dr. Piatak received his Ph.D. in Molecular Virology in 1978 from Yale University. He remained at Yale University for his postdoctoral training in the laboratory of Dr. Sherman Weissman exploring control of RNA synthesis in the Simian Virus 40 infection model. Dr. Piatak then began his career in biotechnology/molecular biology with the Cetus Corporation in 1982 and later joined Genelabs Technologies in 1987. He is a pioneer in the development and application of rigorously quantitative PCR methods to the study of HIV infection, including benchmark studies demonstrating the presence of measurable viremia during all stages of infection and reductions in viremia with implementation of antiretroviral drug treatment. In 1998, Dr. Piatak joined the AIDS and Cancer Virus Program as Head of the Quantitative Molecular Diagnostics Core. Recently, he was also appointed Head of the HIV Molecular Monitoring Core.

Core Descriptions

The Quantitative Molecular Diagnostics Core (QMDC) provides state-of-the-art quantitative molecular analyses to measure specific nucleic acid sequences in specimens provided by laboratories within the ACVP, intramural NIH laboratories, and federally supported studies in extramural laboratories. In particular, the QMDC performs testing for simian immunodeficiency virus and related viruses, with emphasis on determination of viral loads in macaque models of AIDS, including plasma viral loads, cell-associated viral loads and tissue associated viral loads.

In contrast to the situation for HIV-1 viral load analysis, where commercial incentives drove the development of test kits suitable for use in virtually any laboratory, there was no push by the diagnostics industry to develop assay kits for SIV and related viruses based on the perception of a limited market. The QMDC was established to fill the need for viral load testing in the non-human primate models for AIDS related studies. Using quantitative PCR approaches for sequence detection and measurement, combined with near quantitative methods for nucleic acid recovery from specimens, the QMDC has become a recognized leader in the development, application and performance of SIV viral load measurements. The QMDC is distinguished by the breadth of the assays available, including those applied to isolated cells and tissue samples, as well as the willingness and ability to respond to special requests for rapid turnaround of results important to timely decisions for clinical management of study animals and for study protocols, and to provide those services in the most cost-effective manner. The overriding mission objective of the QMDC is to respond to the ever-evolving needs of the research community working on non-human primate models for AIDS for maximally sensitive quantitative nucleic acid diagnostic services, especially assays not available from other sources.

The HIV Molecular Monitoring Core (HMMC) was established in response to the increasing demand for specialized molecular analyses of viral parameters in clinical studies in the AIDS research community. A number of advanced technology assays for HIV viral load determinations and for sequence analysis of individual and populations of virus had been developed by the HIV Drug Resistance Program (DRP) of the Frederick National Laboratory for Cancer Research but were of limited availability to the clinical research community owing to other programmatic demands and responsibilities of the DRP. To make those specialized technologies more accessible as they are developed, HMMC as a separate core facility. At the outset, the key technologies resident in the core will consist of an ultra sensitive viral load assay for HIV-1 (threshold limit of detection <1 HIV-1 RNA copy/mL of plasma), single genome sequencing methods, and analysis of genotypic markers of drug resistance. Newer technologies currently being developed and planned for transition to the core include ultradeep sequencing technology to better characterize HIV diversity, transmission, drug resistance, and evolution, ultra-sensitive detection and quantitation of low-level resistance mutations in non-subtype B virus in infected individuals, genetic and quantitative assays to characterize HIV-1 in tissue specimens, and assays to accurately discriminate and quantitate integrated proviral DNA and circular DNA. In addition, there is consideration for future adaptation/expansion of a number of these and other technologies to the study of other virus infections with broad public health impact, in particular, hepatitis B and C.

The HMMC is not yet completely operational but information on services and access to the same may be had by contacting Dr. Michael Piatak.

Publications

1. Martinelli E, Tharinger H, Frank I, Arthos J, Piatak M Jr, Lifson JD, Blanchard J, Gettie A, Robbiani M. HSV-2 infection of dendritic cells amplifies a highly susceptible HIV-1 cell target. PLoS Pathog. 2011 Jun;7(6):e1002109. Epub 2011 Jun 30. PubMed PMID: 21738472; PubMed Central PMCID: PMC3128120.
2. Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson T, Legasse AW, Chiuchiolo MJ, Parks CL, Axthelm MK, Nelson JA, Jarvis MA, Piatak M Jr, Lifson JD, Picker LJ. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011 May 26;473(7348):523-7. Epub 2011 May 11. PubMed PMID: 21562493; PubMed Central PMCID: PMC3102768.
3. Singer R, Derby N, Rodriguez A, Kizima L, Kenney J, Aravantinou M, Chudolij A, Gettie A, Blanchard J, Lifson JD, Piatak M Jr, Fernández-Romero JA, Zydowsky TM, Robbiani M. The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques. J Virol. 2011 Jun;85(11):5504-12. Epub 2011 Mar 16. PubMed PMID: 21411526; PubMed Central PMCID: PMC3094984.
4. Minang JT, Trivett MT, Barsov EV, Del Prete GQ, Trubey CM, Thomas JA, Gorelick RJ, Piatak M Jr, Ott DE, Ohlen C: TCR triggering transcriptionally downregulates CCR5 expression on rhesus macaque CD4+ T cells with no measurable effect on susceptibility to SIV infection. Virology 409(1):132-140, 2011. Epub 2010 Oct 28. PMID: 21035160
5. Kenney J, Aravantinou M, Singer R, Hsu M, Rodriguez A, Kizima L, Abraham CJ, Menon R, Seidor S, Chudolij A, Gettie A, Blanchard J, Lifson JD, Piatak M Jr, Fernandez-Romero JA, Zydowsky TM, Robbiani M: An antiretroviral/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques. PLoS One 6(1):e15835, 2011. PMID: 21246052
6. Vagenas P, Aravantinou M, Williams VG, Jasny E, Piatak M, Lifson JD, Salazar AM, Blanchard JL, Gettie A, Robbiani M: A tonsillar polyICLC/AT-2 SIV therapeutic vaccine maintains low viremia following antiretroviral therapy cessation. PLoS One 5(9):e12891, 2010. Epub 2010 Sep 21. PMID: 20877632.
7. Bolton DL, Minang JT, Trivett MT, Song K, Tuscher JJ, Li Y, Piatak M Jr, O’Connor D, Lifson JD, Roederer M, Ohlen C: Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous SIV-specific CD8+ T cell clones during acute and chronic infection of rhesus macaques. J Immunol 184(1):303-314, 2010. Epub 2009 Nov 30. PMID: 19949089.
8. Minang JT, Trivett MT, Bolton DL, Trubey CM, Estes JD, Li Y, Smedley J, Pung R, Rosati M, Jalah R, Pavlakis GN, Felber BK, Piatak M Jr, Roederer M, Lifson JD, Ott D, Ohlen C: Distribution, persistence and efficacy of adoptively transferred central and effector memory-derived autologous SIV-specific CD8+ T cell clones in rhesus macaques during acute infection. J Immunol 184(1):315-326, 2010. Epub 2009 Nov 30. PMID: 19949091.
9. Salisch NC, Kaufmann DE, Awad AS, Reeves RK, Tighe DP, Li Y, Piatak M Jr, Lifson JD, Evans DT, Pereyra F, Freeman GJ, Johnson RP: Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1. J Immunol 184(1):476-87, 2010. Epub 2009 Nov 30. PMID: 19949078.
10. Kim WK, Sun Y, Do H, Autissier P, Halpern EF, Piatak M Jr, Lifson JD, Burdo TH, McGrath MS, Williams K: Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage. J Leukoc Biol 87(4):557-567, 2010. Epub 2009 Oct 20. PMID: 19843579.
11. Leone A, Rohankhedkar M, Okoye A, Legasse A, Axthelm MK, Villinger F, Piatak M Jr, Lifson JD, Assouline B, Morre M, Picker LJ, Sodora DL: Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses. J Immunol 185(3):1650-9, 2010. Epub 2010 Jul 9. PMID: 20622118
12. Alpert MD, Rahmberg AR, Neidermyer W, Ng SK, Carville A, Camp JV, Wilson RL, Piatak M Jr, Mansfield KG, Li W, Miller CJ, Lifson JD, Kozlowski PA, Evans DT. Envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge. J Virol 84(20):10748-64, 2010. Epub 2010 Aug 11. PMID: 20702641
13. Pugach P, Krarup A, Gettie A, Kuroda M, Blanchard J, Piatak M Jr, Lifson JD, Trkola A, Robbiani M: In vivo binding and retention of CD4-specific DARPin 57.2 in macaques. PLoS One 5(8):e12455, 2010. Epub 2010 Aug 27. PMID: 20805996.
14. Veazey RS, Ling B, Green LC, Ribka EP, Lifson JD, Piatak MJr, Lederman MM, Mosier D, Offord R, Hartley O: Topically applied recombinant chemokine analogues fully protect macaques from simian-human immunodeficiency virus challenge. J Infect Dis 199:1525-1527, 2009.
15. Pahar B, Lackner AA, Piatak MJr, Lifson JD, Wang X, Das A, Ling B, Montefiori DC, Veazey RS: Control of viremia and maintenance of intestinal (CD4(+) memory T cells in SHIV (162P3) infected macaques after pathogenic SIV (MAC251) challenge. Virology 387:273-284, 2009.
16. Okoye A, Park H, Rohankhedkar M, Coyne-Johnson L, Lum R, Walker JM, Planer SL, Legasse AW, Sylwester AW, Piatak M Jr, Lifson JD, Sodora DL, Villinger F, Axthelm MK, Schmitz JE, Picker LJ: Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis. J Exp Med 206:1575-1588, 2009.
17. Wilson NA, Keele BF, Reed JS, Piaskowski SM, MacNair CE, Bett AJ, Liang X, Wang F, Thoryk E, Heidecker GJ, Cirton MR, Huang L, Lin J, Vitelli S, Ahn CD, Kaizu M, Maness NJ, Reynolds MR, Friedrich TC, Loffredo JT, Rakasz EG, Erickson S, Allison DB, Piatak MJr, Lifson JD, Shiver JW, Casimiro DR, Shaw GM, Hahn BH, Watkins DI: Vaccine-induced cellular responses control SIV replication after heterologous challenge. J Virol 83:6508-6521, 2009.
18. Kader M, Wang X, Piatak M, Lifson J, Roederer M, Veazey R, Mattapallil JJ: Alpha4(+)beta7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol 2:439-449, 2009.
19. Minang JT, Trivett MT, Coren LV, Barsov EV, Piatak MJr, Ott DE, Ohlen C: Nef-mediated MHC class I down-regulation unmasks clonal differences in virus suppression by SIV-specific CD8+ T cells independent of IFN-gamma and CD107a responses. Virology 391:130-139, 2009.
20. Crostarosa F, Aravantinou M, Akpogheneta OJ, Jasny E, Shaw A, Kenney J, Piatak M Jr, Lifson JD, Teitelbaum A, Hu L, Chudolij A, Zydowsky TM, Blanchard J, Gettie A, Robbiani M: A macaque model to study vaginal HSV-2/immunodeficiency virus co-infection and the impact of HSV-2 on microbicide efficacy. PLoS ONE 4(11):e8060, 2009. PMID: 20011586.

Staffing for QMDC

• Yuan Li, M.S., Research Associate III
• Rebecca W. Shoemaker, Research Associate II
• Kelli A. Oswald, Research Associate II
• William Bosche, Research Associate II
• Randy L. Fast, Research Associate I

Staffing for HMMC

• Brandi Freemire, M.S., Research Associate III
• Teresa Shatzer, Research Associate I
• Leslie Lipkey, Research Associate I
• Priyanka Vengurlekar, Bioinformatics Specialist