Lawrence Corey

Trinity Washington University, Washington, Washington, D.C., United States

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Publications (443)4821.88 Total impact

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    ABSTRACT: Background. The management of respiratory virus infections prior to hematopoietic cell transplant (HCT) is difficult. We examined whether respiratory virus detection before HCT influenced the requirement for bronchoscopy, hospitalization, and overall survival following HCT. Methods. Pre-HCT and weekly post-HCT nasal washes were collected through day 100 from patients with and without symptoms. Samples were tested by multiplex polymerase chain reaction for respiratory syncytial virus, parainfluenza viruses 1-4, influenza A and B, human metapneumovirus, adenovirus, and human rhinoviruses, coronaviruses, and bocavirus. Results. Of 458 patients, 116 (25%) had respiratory viruses detected pre-HCT. Overall, patients with viruses detected pre-HCT had fewer days alive and out of the hospital and lower survival at day 100 (adjusted hazard ratio [aHR], 2.4; 95% confidence interval [CI], 1.3-4.5; P = .007) than patients with negative samples; this risk was also present with rhinovirus alone (aHR for mortality, 2.6; 95% CI, 1.2-5.5; P = .01). No difference in bronchoscopy incidence was seen in patients with and without respiratory viruses (aHR, 1.3; 95% CI, .8-2.0; P = .32). In symptomatic patients, those with respiratory viruses detected had increased overall mortality compared with patients without viruses detected (unadjusted HR, 3.5; 95% CI, 1.0-12.1; P = .05); among asymptomatic patients, detection of respiratory viruses was not associated with increased mortality. Conclusions. These data support routine testing for respiratory viruses among symptomatic patients before HCT, and delay of transplant with virus detection when feasible, even for detection of rhinovirus alone. Further study is needed to address whether asymptomatic patients should undergo screening for respiratory virus detection before HCT.
    Clinical Infectious Diseases 04/2015; DOI:10.1093/cid/civ272 · 9.42 Impact Factor
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    ABSTRACT: Background. Despite major advances in the prevention of cytomegalovirus (CMV) disease, the treatment of CMV pneumonia in hematopoietic cell transplant (HCT) recipients remains a significant challenge. Methods. We examined recipient, donor, transplant, viral and treatment factors associated with overall and attributable mortality using Cox regression models. Results. Four hundred twenty-one cases were identified between 1986 and 2011. Overall survival at 6 months was 30% (95% confidence interval 25%-34%). Outcome improved after 2000 (adjusted hazard ratio hazard ratio 0.7, 95% CI 0-5-1.0, p=0.06 [all-cause mortality], adjusted hazard ratio 0.6, 95% CI 0.4-0.9, p=0.01 [attributable mortality]). Factors independently associated with an increased risk of all-cause and attributable mortality included female sex, elevated bilirubin, lymphopenia, and mechanical ventilation; grade 3/4 acute graft versus host disease was associated with all-cause mortality only. An analysis of patients who were transplanted in the current preemptive therapy era (N=233) showed only lymphopenia and mechanical ventilation as significant risk factors for overall and attributable mortality. Antiviral treatment with ganciclovir or foscarnet was associated with improved outcome compared to no antiviral treatment. However, the addition of intravenous pooled or CMV-specific immunoglobulin to antiviral treatment did not seem to improve overall or attributable mortality. Conclusions. Outcome of CMV pneumonia showed a modest improvement over the past 25 years. However, advances seem to be due to antiviral treatment and changes in transplantation practices rather than immunoglobulin-based treatments. Novel treatment strategies for CMV pneumonia are needed.
    Clinical Infectious Diseases 03/2015; 61(1). DOI:10.1093/cid/civ215 · 9.42 Impact Factor
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    ABSTRACT: To evaluate the utility of quantitative herpes simplex virus (HSV) polymerase chain reaction (PCR) levels for prognosis and management of neonatal HSV disease. Clinical and virologic data were abstracted by medical record review from neonatal HSV cases treated at Seattle Children's Hospital between 1993 and 2012. HSV PCR results from plasma (n = 47), cerebrospinal fluid (n = 56), or both (n = 40) at the time of diagnosis were available from 63 infants; 26 with skin-eye-mouth (SEM), 18 with central nervous system (CNS), and 19 with disseminated (DIS) disease. Plasma HSV PCR was positive in 78% of the infants with SEM, 64% with CNS and 100% with DIS disease. Mean plasma viral level was 2.8 log10 copies/mL in SEM, 2.2 log10 copies/mL in CNS, and 7.2 log10 copies/mL in DIS infants. The HSV levels were higher among infants who died compared with surviving infants, 8.1 log10 copies/mL (range 7.7-8.6) vs 3.8 log10 copies/mL (range 0.0-8.6), P = .001, however, level of HSV DNA in the cerebrospinal fluid or in plasma did not correlate with neurologic outcome. Dynamics of HSV clearance from plasma during high-dose acyclovir treatment showed single-phase exponential decay with a median viral half-life of 1.26 days (range: 0.8-1.51). Plasma HSV levels correlate with clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Pediatrics 12/2014; 166(4). DOI:10.1016/j.jpeds.2014.11.011 · 3.74 Impact Factor
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    ABSTRACT: Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Vaccine 10/2014; 33(6). DOI:10.1016/j.vaccine.2014.10.017 · 3.49 Impact Factor
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    AIDS Research and Human Retroviruses 10/2014; 30 Suppl 1:A33-4. DOI:10.1089/aid.2014.5052a.abstract · 2.46 Impact Factor
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    ABSTRACT: Finding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combination of 5 lipopeptides) alone (250 mu g), ALVAC-HIV (vCP1452) alone, or 3 groups of ALVAC-HIV (vCP1452) followed by ALVAC-HIV (vCP1452) plus LIPO-5 (250, 750, and 2,500 mu g). Only 73/174 participants (42%) received all four vaccinations due to a study halt related to myelitis. There were no significant differences in systemic reactions between groups or in local reactogenicity between groups receiving ALVAC-HIV (vCP1452). Significant differences in local reactogenicity occurred between groups receiving LIPO-5 (P <= 0.05). Gag and Env antibodies were undetectable by ELISA 2 weeks after the fourth vaccination for all but one recipient. Antibodies to Gag and Env were present in 32% and 24% of recipients of ALVAC-HIV (vCP1452) alone and in 47% and 35% of ALVAC-HIV (vCP1452) + LIPO recipients, respectively. Coadministration of LIPO-5 did not significantly increase the response rate compared to ALVAC-HIV (vCP1452) alone, nor was there a significant relationship between dose and antibody responses among ALVAC-HIV (vCP1452) + LIPO groups. Over 90% of study participants had no positive gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot assay (ELISpot) responses to any peptide pool at any time point. The study was halted due to a case of myelitis possibly related to the LIPO-5 vaccine; this case of myelitis remains an isolated event. In general, there was no appreciable cell-mediated immunity detected in response to the vaccines used in this study, and antibody responses were limited.
    Clinical and vaccine Immunology: CVI 09/2014; 21(11). DOI:10.1128/CVI.00450-14 · 2.37 Impact Factor
  • Glenda E Gray, Lawrence Corey
    The Journal of Infectious Diseases 08/2014; 211(4). DOI:10.1093/infdis/jiu445 · 5.78 Impact Factor
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    ABSTRACT: Background The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. Methods HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18–35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Findings Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31–42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13–2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2–9·5] for vaccine recipients vs 8·8% [7·1–10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. Interpretation The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines. Funding National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council.
    The Lancet Infectious Diseases 05/2014; 14(5). DOI:10.1016/S1473-3099(14)70020-9 · 19.45 Impact Factor
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    ABSTRACT: Human herpesvirus 8 (HHV8) infection leads to potent activation of nuclear factor kappa B (NFκB) in primary and transformed cells. We used recombinant HHV8 (rKSHV.219) expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2α and red fluorescent protein under an early HHV8 lytic gene promoter T1.1 to monitor replication during infection of human foreskin fibroblasts (HF), noting changes in NFκB activity. In primary HF, NFκB levels do not affect the ability of HHV8 to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell-associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFκB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry, was able to partially overcome the deficiency induced by NFκB inhibitors. Our data indicate that in primary cells, NFκB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFκB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.
    Frontiers in Microbiology 04/2014; 5:129. DOI:10.3389/fmicb.2014.00129 · 3.94 Impact Factor
  • Lawrence Corey, M Juliana McElrath
    Nature medicine 03/2014; 20(3):241-2. DOI:10.1038/nm.3503 · 28.05 Impact Factor
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    Vaccine 01/2014; 32(14). DOI:10.1016/j.vaccine.2014.01.052 · 3.49 Impact Factor
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    ABSTRACT: Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups. Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number, NCT01047540.).
    New England Journal of Medicine 01/2014; 370(3):201-10. DOI:10.1056/NEJMoa1301150 · 54.42 Impact Factor
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    ABSTRACT: BackgroundA safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States. Methods At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24. ResultsIn April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, -25.0%; 95% confidence interval, -121.2 to 29.3; P=0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log(10) copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P=0.28). The vaccine regimen had an acceptable side-effect profile. Conclusions The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.)
    New England Journal of Medicine 10/2013; 369(22). DOI:10.1056/NEJMoa1310566 · 54.42 Impact Factor
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    ABSTRACT: The nucleoside analogues acyclovir (ACV) and famciclovir (FCV) reduce frequency and severity of herpes simplex virus-2 (HSV-2) genital shedding. Yet despite high potency in vitro and lack of induced drug resistance, frequent episodes of breakthrough mucosal shedding occur. We tested a published stochastic, spatial mathematical model of HSV-2 replication and spread, in concert with pharmacokinetic and pharmacodynamics equations, against virologic data from clinical trials of twice-daily acyclovir and famciclovir suppression. The model reproduced the key features of clinical trial data including genital shedding episode rate, expansion and decay dynamics, and heterogeneous peak viral production and duration. In simulations, these agents shortened episode duration by limiting extent of viral production by 1-2 logs and limiting formation of secondary ulcers by ∼50%. However, drug concentrations were non-inhibitory during 42% of the dosing cycle. Even if drug concentrations were high at episode initiation, prolonged episodes often ensued due to drug decay over ensuing hours and subsequent rebound of rapidly replicating HSV-2. Local CD8+ T-cell density was more predictive of episode viral production (R(2)=0.42) and duration (R(2)=0.21) than drug concentration at episode onset (R(2)=0.14 and 0.05, respectively), though the model projected that an agent with equivalent potency but two times longer half-life would decrease shedding by 80% compared to standard twice-daily regimens. Therefore, long half-life is a key characteristic of any agent that might fully suppress HSV-2 reactivations.
    Antimicrobial Agents and Chemotherapy 09/2013; DOI:10.1128/AAC.01114-13 · 4.45 Impact Factor
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    ABSTRACT: Experimental and computational evidence suggests that HLAs preferentially bind conserved regions of viral proteins, a concept we term "targeting efficiency," and that this preference may provide improved clearance of infection in several viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were measured from peripheral blood mononuclear cells obtained from a household cohort study performed during the 2009-2010 influenza season. We found that HLA targeting efficiency scores significantly correlated with IFN-γ enzyme-linked immunosorbent spot responses (P = 0.042, multiple regression). A further population-based analysis found that the carriage frequencies of the alleles with the lowest targeting efficiencies, A*24, were associated with pH1N1 mortality (r = 0.37, P = 0.031) and are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use are associated with CD8 T-cell magnitude in humans after influenza infection. The computational tools used in this study may be useful predictors of potential morbidity and identify immunologic differences of new variant influenza strains more accurately than evolutionary sequence comparisons. Population-based studies of the relative frequency of these alleles in severe vs. mild influenza cases might advance clinical practices for severe H1N1 infections among genetically susceptible populations.
    Proceedings of the National Academy of Sciences 07/2013; DOI:10.1073/pnas.1221555110 · 9.81 Impact Factor
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    ABSTRACT: Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.
    PLoS Pathogens 06/2013; 9(6):e1003404. DOI:10.1371/journal.ppat.1003404 · 8.06 Impact Factor
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    ABSTRACT: HIV-1 DNA in blood monocytes is considered a viral source of various HIV-1 infected tissue macrophages, which is also known as "Trojan horse" hypothesis. However, whether these DNA can produce virions has been an open question for years, due to the inability of isolating high titer and infectious HIV-1 directly from monocytes. In this study, we demonstrated successful isolation of two strains of M-HIV-1 (1690 M and 1175 M) from two out of four study subjects, together with their in vivo controls, HIV-1 isolated from CD4+ T-cells (T-HIV-1), 1690 T and 1175 T. All M- and T- HIV-1 isolates were detected CCR5-tropic. Both M- HIV-1 exhibited higher levels of replication in monocyte-derived macrophages (MDM) than the two T- HIV-1. Consistent with our previous reports on the subject 1175 with late infection, compartmentalized env C2-V3-C3 sequences were identified between 1175 M and 1175 T. In contrast, 1690 M and 1690 T, which were isolated from subject 1690 with relatively earlier infection, showed homogenous env C2-V3-C3 sequences. However, multiple reverse transcriptase (RT) inhibitor resistance-associated variations were detected in the Gag-Pol region of 1690 M, but not of 1690 T. By further measuring HIV DNA intracellular copy numbers post-MDM infection, 1690 M was found to have significantly higher DNA synthesis efficiency than 1690 T in macrophages, indicating a higher RT activity, which was confirmed by AZT inhibitory assays. These results suggested that the M- and T- HIV-1 are compartmentalized in the two study subjects, respectively. Therefore, we demonstrated that under in vitro conditions, HIV-1 infected human monocytes can productively release live viruses while differentiating into macrophages.
    PLoS ONE 05/2013; 8(5):e65071. DOI:10.1371/journal.pone.0065071 · 3.53 Impact Factor
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    ABSTRACT: Human metapneumovirus (HMPV), a common respiratory virus, can cause severe disease in pre- and post-hematopoietic cell transplant (HCT) recipients. We conducted a retrospective cohort analysis in HCT patients with HMPV (N=23) or respiratory syncytial virus (RSV, N=23) detected in bronchoalveolar lavage (BAL) samples by reverse-transcription PCR between 2006 and 2011 to determine disease characteristics and factors associated with outcome. Mortality rates at 100 days were 43% for both HMPV and RSV lower respiratory tract disease (LRTD). Steroid therapy, oxygen requirement > 2L or mechanical ventilation and bone marrow as cell source were significant risk factors for overall and virus-related mortality in multivariable models while the virus type was not. The presence of centrilobular/nodular radiographic infiltrates was a possible protective factor for mechanical ventilation. Thus, HMPV LRTD is associated with high mortality in HCT recipients. Earlier detection in combination with new antiviral therapy is needed to reduce mortality among HCT recipients.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2013; 19(8). DOI:10.1016/j.bbmt.2013.05.005 · 3.35 Impact Factor
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    ABSTRACT: Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown that CD8(+) T cells persist in genital skin and mucosa at the dermal-epidermal junction (DEJ)-the portal of neuronal release of reactivating virus-for prolonged time periods after herpes lesions are cleared. The phenotype and function of this persistent CD8(+) T-cell population remain unknown. Here, using cell-type-specific laser capture microdissection, transcriptional profiling and T-cell antigen receptor β-chain (TCRβ) genotyping on sequential genital skin biopsies, we show that CD8αα(+) T cells are the dominant resident population of DEJ CD8(+) T cells that persist at the site of previous HSV-2 reactivation. CD8αα(+) T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. Sequencing of the TCR β-chain repertoire reveals that the DEJ CD8αα(+) T cells are oligoclonal with diverse usage of TCR variable-β genes, which differ from those commonly described for mucosa-associated invariant T cells and natural killer T cells. Dominant clonotypes are shown to overlap among multiple recurrences over a period of two-and-a-half years. Episodes of rapid asymptomatic HSV-2 containment were also associated with a high CD8 effector-to-target ratio and focal enrichment of CD8αα(+) T cells. These studies indicate that DEJ CD8αα(+) T cells are tissue-resident cells that seem to have a fundamental role in immune surveillance and in initial containment of HSV-2 reactivation in human peripheral tissue. Elicitation of CD8αα(+) T cells may be a critical component for developing effective vaccines against skin and mucosal infections.
    Nature 05/2013; 497(7450). DOI:10.1038/nature12110 · 42.35 Impact Factor

Publication Stats

27k Citations
4,821.88 Total Impact Points

Institutions

  • 2015
    • Trinity Washington University
      Washington, Washington, D.C., United States
  • 1987–2015
    • Fred Hutchinson Cancer Research Center
      • • Division of Clinical Research
      • • Division of Vaccine and Infectious Disease
      • • Division of Public Health Sciences
      Seattle, Washington, United States
  • 1982–2014
    • University of Washington Seattle
      • • Department of Medicine
      • • Department of Laboratory Medicine
      • • Division of Allergy and Infectious Diseases
      • • Department of Microbiology
      • • Department of Obstetrics and Gynecology
      • • Department of Pediatrics
      Seattle, Washington, United States
  • 2012
    • University of Wisconsin - Stout
      Menominee, Wisconsin, United States
  • 2008
    • Seattle University
      Seattle, Washington, United States
  • 2007
    • Dartmouth–Hitchcock Medical Center
      Lebanon, New Hampshire, United States
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      North Carolina, United States
    • Cambridge Eco
      Cambridge, England, United Kingdom
  • 1997–2005
    • Duke University Medical Center
      • • Department of Surgery
      • • Department of Obstetrics and Gynecology
      Durham, NC, United States
  • 2004
    • Johns Hopkins University
      • Division of Infectious Diseases
      Baltimore, Maryland, United States
  • 2001–2003
    • University of California, Irvine
      Irvine, California, United States
  • 2002
    • University of Utah
      • Department of Pediatrics
      Salt Lake City, UT, United States
  • 1995
    • Centers for Disease Control and Prevention
      Atlanta, Michigan, United States
  • 1984
    • Stanford Medicine
      • Department of Pediatrics
      Stanford, California, United States