Daniel, M.D., Kirchhoff, F., Czajak, S.C., Sehgal, P.K. & Desrosiers, R.C. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258, 1938–1941 (1992).
Johnson, R.P. & Desrosiers, R.C. Protective immunity induced by live attenuated simian immunodeficiency virus. Curr. Opin. Immunol. 10, 436–443 (1998).
Koff, W.C. et al. HIV vaccine design: insights from live attenuated SIV vaccines. Nat. Immunol. 7, 19–23 (2006).
Picker, L.J., Hansen, S.G. & Lifson, J.D. New paradigms for HIV/AIDS vaccine development. Annu. Rev. Med. 63, 95–111 (2012).
Abel, K. et al. Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and α interferon responses. J. Virol. 77, 3099–3118 (2003).
Sugimoto, C. et al. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV. PLoS ONE 5, e11678 (2010).
Whitney, J.B. & Ruprecht, R.M. Live attenuated HIV vaccines: pitfalls and prospects. Curr. Opin. Infect. Dis. 17, 17–26 (2004).
Metzner, K.J. et al. Effects of in vivo CD8+ T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J. Exp. Med. 191, 1921–1931 (2000).
Stebbings, R. et al. Vaccination with live attenuated simian immunodeficiency virus for 21 days protects against superinfection. Virology 330, 249–260 (2004).
Stebbings, R. et al. CD8+ lymphocytes do not mediate protection against acute superinfection 20 days after vaccination with a live attenuated simian immunodeficiency virus. J. Virol. 79, 12264–12272 (2005).
Nethe, M., Berkhout, B. & van der Kuyl, A.C. Retroviral superinfection resistance. Retrovirology 2, 52 (2005).
Schmitz, J.E. et al. Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239Δ3-vaccinated rhesus macaques. J. Virol. 79, 8131–8141 (2005).
Reynolds, M.R. et al. Macaques vaccinated with live-attenuated SIV control replication of heterologous virus. J. Exp. Med. 205, 2537–2550 (2008).
Mansfield, K. et al. Vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the periphery. J. Virol. 82, 4135–4148 (2008).
Genescà, M. et al. With minimal systemic T-cell expansion, CD8+ T cells mediate protection of rhesus macaques immunized with attenuated simian-human immunodeficiency virus SHIV89.6 from vaginal challenge with simian immunodeficiency virus. J. Virol. 82, 11181–11196 (2008).
Reynolds, M.R. et al. Macaques vaccinated with simian immunodeficiency virus SIVmac239Δ nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge. J. Virol. 84, 9190–9199 (2010).
Haase, A.T. Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu. Rev. Med. 62, 127–139 (2011).
Johnson, R.P. et al. Highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation. J. Virol. 73, 4952–4961 (1999).
Jia, B. et al. Immunization with single-cycle SIV significantly reduces viral loads after an intravenous challenge with SIV(mac)239. PLoS Pathog. 5, e1000272 (2009).
Kirmaier, A. et al. TRIM5 suppresses cross-species transmission of a primate immunodeficiency virus and selects for emergence of resistant variants in the new species. PLoS Biol. 8, e1000462 (2010).
Crotty, S. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29, 621–663 (2011).
Ma, C.S. et al. Early commitment of naive human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL-12. Immunol. Cell Biol. 87, 590–600 (2009).
Hong, J.J., Amancha, P.K., Rogers, K., Ansari, A.A. & Villinger, F. Spatial alterations between CD4+ T follicular helper, B, and CD8+ T cells during simian immunodeficiency virus infection: T/B cell homeostasis, activation, and potential mechanism for viral escape. J. Immunol. 188, 3247–3256 (2012).
Sugimoto, C. et al. nef gene is required for robust productive infection by simian immunodeficiency virus of T-cell–rich paracortex in lymph nodes. J. Virol. 77, 4169–4180 (2003).
West, E.E. et al. Tight regulation of memory CD8+ T cells limits their effectiveness during sustained high viral load. Immunity 35, 285–298 (2011).
Kallies, A. Distinct regulation of effector and memory T-cell differentiation. Immunol. Cell Biol. 86, 325–332 (2008).
Intlekofer, A.M. et al. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat. Immunol. 6, 1236–1244 (2005).
Taylor, J.J. & Jenkins, M.K. CD4+ memory T cell survival. Curr. Opin. Immunol. 23, 319–323 (2011).
Kersse, K., Lamkanfi, M., Bertrand, M.J., Vanden Berghe, T. & Vandenabeele, P. Interaction patches of procaspase-1 caspase recruitment domains (CARDs) are differently involved in procaspase-1 activation and receptor-interacting protein 2 (RIP2)-dependent nuclear factor κB signaling. J. Biol. Chem. 286, 35874–35882 (2011).
Verdeil, G., Puthier, D., Nguyen, C., Schmitt-Verhulst, A.-M. & Auphan-Anezin, N. STAT5-mediated signals sustain a TCR-initiated gene expression program toward differentiation of CD8 T cell effectors. J. Immunol. 176, 4834–4842 (2006).
Coller, H.A., Sang, L. & Roberts, J.M. A new description of cellular quiescence. PLoS Biol. 4, e83 (2006).
Sacha, J.B. et al. Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proc. Natl. Acad. Sci. USA 106, 9791–9796 (2009).
Sant, A.J. & McMichael, A. Revealing the role of CD4+ T cells in viral immunity. J. Exp. Med. 209, 1391–1395 (2012).
Hansen, S.G. et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473, 523–527 (2011).
Haynes, B.F. et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366, 1275–1286 (2012).
Barouch, D.H. et al. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 482, 89–93 (2012).
Vezys, V. et al. Memory CD8 T-cell compartment grows in size with immunological experience. Nature 457, 196–199 (2009).
Pitcher, C.J. et al. Development and homeostasis of T cell memory in rhesus macaque. J. Immunol. 168, 29–43 (2002).
Grossman, Z. & Picker, L.J. Pathogenic mechanisms in simian immunodeficiency virus infection. Curr. Opin. HIV AIDS 3, 380–386 (2008).
Shen, A. et al. Novel pathway for induction of latent virus from resting CD4+ T cells in the simian immunodeficiency virus/macaque model of human immunodeficiency virus type 1 latency. J. Virol. 81, 1660–1670 (2007).
Chackerian, B., Haigwood, N.L. & Overbaugh, J. Characterization of a CD4-expressing macaque cell line that can detect virus after a single replication cycle and can be infected by diverse simian immunodeficiency virus isolates. Virology 213, 386–394 (1995).
Veazey, R.S. et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280, 427–431 (1998).
Schmitz, J.E. et al. Simian immunodeficiency virus (SIV)-specific CTL are present in large numbers in livers of SIV-infected rhesus monkeys. J. Immunol. 164, 6015–6019 (2000).
Cline, A.N., Bess, J.W., Piatak, M. Jr. & Lifson, J.D. Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J. Med. Primatol. 34, 303–312 (2005).
Venneti, S. et al. Longitudinal in vivo positron emission tomography imaging of infected and activated brain macrophages in a macaque model of human immunodeficiency virus encephalitis correlates with central and peripheral markers of encephalitis and areas of synaptic degeneration. Am. J. Pathol. 172, 1603–1616 (2008).
Salisch, N.C. et al. Inhibitory TCR coreceptor PD-1 is a sensitive indicator of low-level replication of SIV and HIV-1. J. Immunol. 184, 476–487 (2010).
Martins, M.A. et al. T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge. J. Virol. 84, 4352–4365 (2010).
Hansen, S.G. et al. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat. Med. 15, 293–299 (2009).
Walker, J.M., Maecker, H.T., Maino, V.C. & Picker, L.J. Multicolor flow cytometric analysis in SIV-infected rhesus macaque. Methods Cell Biol. 75, 535–557 (2004).
Picker, L.J. et al. IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates. J. Clin. Invest. 116, 1514–1524 (2006).
Picker, L.J. et al. Control of lymphocyte recirculation in man. I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition. J. Immunol. 150, 1105–1121 (1993).
Todd, C.A. et al. Development and implementation of an international proficiency testing program for a neutralizing antibody assay for HIV-1 in TZM-bl cells. J. Immunol. Methods 375, 57–67 (2012).
Pollara, J. et al. High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses. Cytometry A 79, 603–612 (2011).
R Core Team. R: a language and environment for statistical computing. <http://www.r-project.org/> (2011).
Gentleman, R.C. et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).
Smyth, G.K. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, 3 (2004).
Caskey, M. et al. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J. Exp. Med. 208, 2357–2366 (2011).
Wolfe, D.A. & Hollander, M. Nonparametric Statistical Methods. (Wiley, New York, 1973).