Experts and Doctors on lymphocytic choriomeningitis virus in Atlanta, Georgia, United States


Locale: Atlanta, Georgia, United States
Topic: lymphocytic choriomeningitis virus

Top Publications

  1. Harrington L, Galvan M, Baum L, Altman J, Ahmed R. Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. J Exp Med. 2000;191:1241-6 pubmed
    ..This latter information will be of value in optimizing immunization strategies for boosting CD8 T cell responses. ..
  2. Silverman M, Pearce B, Biron C, Miller A. Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol. 2005;18:41-78 pubmed
  3. Amman B, Pavlin B, Albarino C, Comer J, Erickson B, Oliver J, et al. Pet rodents and fatal lymphocytic choriomeningitis in transplant patients. Emerg Infect Dis. 2007;13:719-25 pubmed
    ..This report details the animal traceback and the supporting laboratory investigations. ..
  4. Vezys V, Masopust D, Kemball C, Barber D, O Mara L, Larsen C, et al. Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med. 2006;203:2263-9 pubmed
    ..These findings reveal a novel role for antigen in maintaining virus-specific CD8 T cells during persistent infection and provide insight toward understanding T cell differentiation in chronic infection. ..
  5. Wherry E, Teichgräber V, Becker T, Masopust D, Kaech S, Antia R, et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 2003;4:225-34 pubmed
    ..We propose that T(CM) and T(EM) do not necessarily represent distinct subsets, but are part of a continuum in a linear naive --> effector --> T(EM) --> T(CM) differentiation pathway. ..
  6. Williams M, Onami T, Adams A, Durham M, Pearson T, Ahmed R, et al. Cutting edge: persistent viral infection prevents tolerance induction and escapes immune control following CD28/CD40 blockade-based regimen. J Immunol. 2002;169:5387-91 pubmed
  7. Wherry E, Barber D, Kaech S, Blattman J, Ahmed R. Antigen-independent memory CD8 T cells do not develop during chronic viral infection. Proc Natl Acad Sci U S A. 2004;101:16004-9 pubmed
    ..These findings raise concerns about using vaccines that may persist and also suggest that there may be limitations and challenges in designing effective immunological interventions for the treatment of chronic infections and tumors. ..
  8. van der Most R, Murali Krishna K, Lanier J, Wherry E, Puglielli M, Blattman J, et al. Changing immunodominance patterns in antiviral CD8 T-cell responses after loss of epitope presentation or chronic antigenic stimulation. Virology. 2003;315:93-102 pubmed
    ..A model in which recruitment time plays a role in the longevity of antiviral T-cell responses during persistent infection is discussed. ..
  9. Becker T, Coley S, Wherry E, Ahmed R. Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells. J Immunol. 2005;174:1269-73 pubmed
    ..These results show that the bone marrow is not only the source of stem cells for generating naive T cells but also provides the necessary signals for the self-renewal of memory T cells. ..

More Information


  1. Barber D, Wherry E, Ahmed R. Cutting edge: rapid in vivo killing by memory CD8 T cells. J Immunol. 2003;171:27-31 pubmed
    ..These data indicate that virus specific memory CD8 T cells can rapidly acquire cytotoxic function upon re-exposure to Ag and are much more efficient killers in vivo than previously appreciated. ..
  2. Sarkar S, Kalia V, Haining W, Konieczny B, Subramaniam S, Ahmed R. Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J Exp Med. 2008;205:625-40 pubmed publisher
    ..These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation. ..
  3. Yates A, Graw F, Barber D, Ahmed R, Regoes R, Antia R. Revisiting estimates of CTL killing rates in vivo. PLoS ONE. 2007;2:e1301 pubmed
    ..We discuss extensions to the basic CTL killing model to explain this discrepancy and propose experimental tests to distinguish between them. ..
  4. Suresh M, Whitmire J, Harrington L, Larsen C, Pearson T, Altman J, et al. Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory. J Immunol. 2001;167:5565-73 pubmed
    ..Therefore, CD28 signaling is not necessary for the proliferative renewal and maintenance of memory CD8 T cells. ..
  5. Blattman J, Antia R, Sourdive D, Wang X, Kaech S, Murali Krishna K, et al. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J Exp Med. 2002;195:657-64 pubmed
    ..Thus, an acute LCMV infection results in a >1,000-fold increase in precursor frequency of D(b)GP33-specific CD8 T cells from 2 x 10(2) naive cells in uninfected mice to 5 x 10(5) memory cells in immunized mice. ..
  6. Wherry E, Ha S, Kaech S, Haining W, Sarkar S, Kalia V, et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007;27:670-84 pubmed
    ..Thus, functional exhaustion is probably due to both active suppression and passive defects in signaling and metabolism. These results provide a framework for designing rational immunotherapies during chronic infections. ..
  7. Chavan R, Marfatia K, An I, Garber D, Feinberg M. Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses. J Virol. 2006;80:7676-87 pubmed
    ..Our results demonstrate that a strategy to express specific genetic adjuvants from rMVA vectors can be successfully applied to enhance the immunogenicity of MVA-based vaccines. ..
  8. West E, Jin H, Rasheed A, Penaloza MacMaster P, Ha S, Tan W, et al. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest. 2013;123:2604-15 pubmed publisher
    ..These results suggest that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer. ..
  9. Mueller S, Langley W, Carnero E, Garcia Sastre A, Ahmed R. Immunization with live attenuated influenza viruses that express altered NS1 proteins results in potent and protective memory CD8+ T-cell responses. J Virol. 2010;84:1847-55 pubmed publisher
    ..These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines. ..
  10. Mueller S, Langley W, Li G, Garcia Sastre A, Webby R, Ahmed R. Qualitatively different memory CD8+ T cells are generated after lymphocytic choriomeningitis virus and influenza virus infections. J Immunol. 2010;185:2182-90 pubmed publisher
    ..These findings suggest that qualitatively different memory CD8(+) T cells are generated after respiratory or systemic virus infections...
  11. Langley W, Bradley K, Li Z, Talekar G, Galloway S, Steinhauer D. The effects of preexisting immunity to influenza on responses to influenza vectors in mice. Vaccine. 2010;28:6305-13 pubmed publisher
    ..These CD8(+) T cells were further shown to protect mice from a lethal challenge by a heterologous influenza subtype. The implication of these data for the use of influenza virus vectors and influenza vaccination in general are discussed...
  12. Iyer S, Chatraw J, Tan W, Wherry E, Becker T, Ahmed R, et al. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells. J Immunol. 2012;188:77-84 pubmed publisher
    ..The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals. ..
  13. Murali Krishna K, Lau L, Sambhara S, Lemonnier F, Altman J, Ahmed R. Persistence of memory CD8 T cells in MHC class I-deficient mice. Science. 1999;286:1377-81 pubmed
    ..Thus, after naïve CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance. ..
  14. Crotty S, Kersh E, Cannons J, Schwartzberg P, Ahmed R. SAP is required for generating long-term humoral immunity. Nature. 2003;421:282-7 pubmed
    ..Thus, SAP has a crucial role in CD4+ T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching. ..
  15. Tan J, Whitmire J, Murali Krishna K, Ahmed R, Altman J, Mittler R, et al. 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. J Immunol. 2000;164:2320-5 pubmed
  16. Auperin D, McCormick J. Nucleotide sequence of the Lassa virus (Josiah strain) S genome RNA and amino acid sequence comparison of the N and GPC proteins to other arenaviruses. Virology. 1989;168:421-5 pubmed
    ..These findings reveal that the G2 envelope glycoprotein is more conserved among different arenaviruses than the internal nucleoprotein...
  17. Kaech S, Tan J, Wherry E, Konieczny B, Surh C, Ahmed R. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol. 2003;4:1191-8 pubmed
    ..Thus, selective expression of IL-7R identifies memory cell precursors, and this marker may be useful in predicting the number of memory T cells generated after infection or immunization...
  18. Blattman J, Wherry E, Ha S, van der Most R, Ahmed R. Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection. J Virol. 2009;83:4386-94 pubmed publisher
  19. Tan J, Whitmire J, Ahmed R, Pearson T, Larsen C. 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J Immunol. 1999;163:4859-68 pubmed
  20. Choo D, Murali Krishna K, Anita R, Ahmed R. Homeostatic turnover of virus-specific memory CD8 T cells occurs stochastically and is independent of CD4 T cell help. J Immunol. 2010;185:3436-44 pubmed publisher
  21. Aneja R, Kalia V, Ahmed R, Joshi H. Nonimmunosuppressive chemotherapy: EM011-treated mice mount normal T-cell responses to an acute lymphocytic choriomeningitis virus infection. Mol Cancer Ther. 2007;6:2891-9 pubmed
    ..These data provide compelling evidence to support the nonimmunosuppressive nature of EM011 therapy and provide strong impetus for combining chemotherapy with immunotherapy as a novel anticancer strategy...
  22. Sarkar S, Teichgräber V, Kalia V, Polley A, Masopust D, Harrington L, et al. Strength of stimulus and clonal competition impact the rate of memory CD8 T cell differentiation. J Immunol. 2007;179:6704-14 pubmed
    ..Thus, long-lasting, Ag-independent CD8 T cell memory results from progressive differentiation of memory CD8 T cells, and the rate of memory T cell differentiation is governed by events occurring early during T cell priming. ..
  23. Suresh M, Lanier G, Large M, Whitmire J, Altman J, Ruddle N, et al. Role of lymphotoxin alpha in T-cell responses during an acute viral infection. J Virol. 2002;76:3943-51 pubmed
    ..These results showed that impairment in the activation of LCMV-specific T cells in LTalpha(-/-) mice may be due to abnormal lymphoid architecture and not to an intrinsic defect in LTalpha(-/-) T cells. ..
  24. Penaloza MacMaster P, Ur Rasheed A, Iyer S, Yagita H, Blazar B, Ahmed R. Opposing effects of CD70 costimulation during acute and chronic lymphocytic choriomeningitis virus infection of mice. J Virol. 2011;85:6168-74 pubmed publisher
    ..Tailored triggering or blockade of this costimulatory pathway may be important in vaccination regimens against acute or chronic pathogens. ..
  25. West E, Youngblood B, Tan W, Jin H, Araki K, Alexe G, et al. Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load. Immunity. 2011;35:285-98 pubmed publisher
    ..Thus, emphasizing the importance of designing vaccines that elicit effective CD4(+) T cell help and rapidly control infection. ..
  26. Vezys V, Masopust D, Desmarets M, Wess J, Zimring J. Analysis of CD8+ T cell-mediated anti-viral responses in mice with targeted deletions of the M1 or M5 muscarinic cholinergic receptors. Life Sci. 2007;80:2330-3 pubmed
  27. Miller J, Peters M, Oran A, Beresford G, Harrington L, Boss J, et al. CD94/NKG2 expression does not inhibit cytotoxic function of lymphocytic choriomeningitis virus-specific CD8+ T cells. J Immunol. 2002;169:693-701 pubmed
    ..Finally, down-regulation of CD94/NKG2 was found to occur only during chronic LCMV infection. Altogether, this study suggests that CD94/NKG2 expression is not necessarily correlated with inhibition of T cell function. ..
  28. Wherry E, Becker T, Boone D, Kaja M, Ma A, Ahmed R. Homeostatic proliferation but not the generation of virus specific memory CD8 T cells is impaired in the absence of IL-15 or IL-15Ralpha. Adv Exp Med Biol. 2002;512:165-75 pubmed
    ..Together these results suggest that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time. ..
  29. Chappell C, Beard C, Altman J, Jaenisch R, Jacob J. DNA methylation by DNA methyltransferase 1 is critical for effector CD8 T cell expansion. J Immunol. 2006;176:4562-72 pubmed
    ..Our data suggest that ablation of Dnmt1 and subsequent DNA methylation affect the finite proliferative potential of Ag-specific CD8+ T cells with moderate effects on their differentiation to effector and memory CD8+ T cells. ..
  30. Duraiswamy J, Ibegbu C, Masopust D, Miller J, Araki K, Doho G, et al. Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults. J Immunol. 2011;186:4200-12 pubmed publisher
    ..In conclusion, our study shows that most PD-1(hi) CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells. ..
  31. Araki K, Gangappa S, Dillehay D, Rouse B, Larsen C, Ahmed R. Pathogenic virus-specific T cells cause disease during treatment with the calcineurin inhibitor FK506: implications for transplantation. J Exp Med. 2010;207:2355-67 pubmed publisher
    ..Furthermore, we identify a potential strategy (blockade of TNF and IL-6) for treatment of transplant recipients who have acute complications of viral infection...
  32. Norris B, Uebelhoer L, Nakaya H, Price A, Grakoui A, Pulendran B. Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity. Immunity. 2013;38:309-21 pubmed publisher
    ..The reduction of monocytic cells in Ccr2(-/-) mice or after Gr-1 antibody depletion enhanced antiviral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection...
  33. Hale J, Youngblood B, Latner D, Mohammed A, Ye L, Akondy R, et al. Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection. Immunity. 2013;38:805-17 pubmed publisher
    ..These findings have important implications for rational vaccine design, where improving the generation and engagement of memory Tfh cells could be used to enhance vaccine-induced protective immunity. ..
  34. Zajac A, Vance R, Held W, Sourdive D, Altman J, Raulet D, et al. Impaired anti-viral T cell responses due to expression of the Ly49A inhibitory receptor. J Immunol. 1999;163:5526-34 pubmed
    ..Overall, these studies demonstrate that expression of killer inhibitory receptors can modulate anti-viral T cell responses in vivo and in vitro. ..
  35. Araki K, Turner A, Shaffer V, Gangappa S, Keller S, Bachmann M, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460:108-12 pubmed publisher
    ..Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T cells. ..
  36. Mueller S, Hosiawa Meagher K, Konieczny B, Sullivan B, Bachmann M, Locksley R, et al. Regulation of homeostatic chemokine expression and cell trafficking during immune responses. Science. 2007;317:670-4 pubmed
    ..We propose that this transient chemokine modulation may help orchestrate local cellularity, thus minimizing competition for space and resources in activated lymphoid tissues. ..
  37. Maris C, Miller J, Altman J, Jacob J. A transgenic mouse model genetically tags all activated CD8 T cells. J Immunol. 2003;171:2393-401 pubmed
    ..We show that in this transgenic mouse model system, all of the antiviral effector and memory CD8+ T cells are contained within the beta-gal-marked CD8+ T cell population. ..
  38. Zhang B, Zhang Y, Niu L, Vella A, Mittler R. Dendritic cells and Stat3 are essential for CD137-induced CD8 T cell activation-induced cell death. J Immunol. 2010;184:4770-8 pubmed publisher
    ..Taken together, these data suggest that CD137 signaling in DCs can regulate CD8 T cell survival through a Stat3 and Fas-mediated pathway. ..
  39. Ha S, Mueller S, Wherry E, Barber D, Aubert R, Sharpe A, et al. Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. J Exp Med. 2008;205:543-55 pubmed publisher
    ..Such an approach may have broad applications in developing treatment strategies for chronic infections in general, and perhaps also for tumors...
  40. Jin H, Anderson A, Tan W, West E, Ha S, Araki K, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107:14733-8 pubmed publisher
  41. Dauner J, Williams I, Jacob J. Differential microenvironment localization of effector and memory CD8 T cells. J Immunol. 2008;180:291-9 pubmed
    ..Upon rechallenge, memory CD8 T cells rapidly proliferate and the secondary effector CD8 T cells are found in the red pulp. ..
  42. Onami T, Harrington L, Williams M, Galvan M, Larsen C, Pearson T, et al. Dynamic regulation of T cell immunity by CD43. J Immunol. 2002;168:6022-31 pubmed
    ..These data suggest a dynamic role of CD43 during an immune response: a positive regulatory role in costimulation and trafficking of T cells to the CNS and a negative regulatory role in the down-modulation of an immune response. ..
  43. Whitmire J, Flavell R, Grewal I, Larsen C, Pearson T, Ahmed R. CD40-CD40 ligand costimulation is required for generating antiviral CD4 T cell responses but is dispensable for CD8 T cell responses. J Immunol. 1999;163:3194-201 pubmed
    ..This study highlights the importance of CD40-CD40L interactions in generating virus-specific CD4 T cell responses and in resolving chronic viral infection. ..
  44. Aubert R, Kamphorst A, Sarkar S, Vezys V, Ha S, Barber D, et al. Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection. Proc Natl Acad Sci U S A. 2011;108:21182-7 pubmed publisher
    ..These results suggest that CD4 T-cell immunotherapy alone or in conjunction with blockade of inhibitory receptors may be a promising approach for treating CD8 T-cell dysfunction in chronic infections and cancer. ..
  45. Albarino C, Palacios G, Khristova M, Erickson B, Carroll S, Comer J, et al. High diversity and ancient common ancestry of lymphocytic choriomeningitis virus. Emerg Infect Dis. 2010;16:1093-100 pubmed publisher
    ..Bayesian analysis estimates the most recent common ancestor to be 1,000-5,000 years old, and this long history is consistent with complex phylogeographic relationships of the extant virus isolates...
  46. Murali Krishna K, Ahmed R. Cutting edge: naive T cells masquerading as memory cells. J Immunol. 2000;165:1733-7 pubmed
    ..In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules. ..
  47. Sosa L, Gupta S, Juthani Mehta M, Hadler J. Meningitis in a college student in Connecticut, 2007. J Am Coll Health. 2009;58:12-4 pubmed publisher
    ..The authors also provide a review of LCMV infection, epidemiology, and public health implications. Providers should be aware of LCMV as a cause of meningitis in college students, especially those with a history of rodent exposure. ..
  48. Vezys V, Penaloza MacMaster P, Barber D, Ha S, Konieczny B, Freeman G, et al. 4-1BB signaling synergizes with programmed death ligand 1 blockade to augment CD8 T cell responses during chronic viral infection. J Immunol. 2011;187:1634-42 pubmed publisher
    ..These findings demonstrate the importance of carefully manipulating the balance between activating and inhibitory signals to enhance T cell responses during chronic infection. ..
  49. Loria G, Romagnoli P, Moseley N, Rucavado A, Altman J. Platelets support a protective immune response to LCMV by preventing splenic necrosis. Blood. 2013;121:940-50 pubmed publisher
    ..These data suggest that, by their supportive roles in hemostasis, platelets may be preventing the severe pathology observed in human arenaviral infections. ..
  50. Nayak B, Sailaja G, Jabbar A. Augmenting the immunogenicity of DNA vaccines: role of plasmid-encoded Flt-3 ligand, as a molecular adjuvant in genetic vaccination. Virology. 2006;348:277-88 pubmed
  51. Barber D, Wherry E, Masopust D, Zhu B, Allison J, Sharpe A, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439:682-7 pubmed
    ..These studies identify a specific mechanism of T-cell exhaustion and define a potentially effective immunological strategy for the treatment of chronic viral infections. ..
  52. Constantin C, Masopust D, Gourley T, Grayson J, Strickland O, Ahmed R, et al. Normal establishment of virus-specific memory CD8 T cell pool following primary infection during pregnancy. J Immunol. 2007;179:4383-9 pubmed
    ..These data suggest that virus-specific adaptive memory is normally generated in mice during pregnancy. ..