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Background: The National Institutes of Health (NIH) Loan Repayment Programs (LRPs) were established by Congress in 2000 to help attract and retain highly qualified health professionals in biomedical careers by relieving financial pressure incurred from educational loans obtained during medical school and other advanced-degree clinical training programs. In 2019, the NIH LRP Program increased the maximum repayment from $35,000 per year to $50,000 per year for an individual's educational debt in return for two years of research performed in an NIH mission-relevant area (https://www.lrp.nih.gov/eligibility-programs). In addition, in 2020, the National Heart, Lung, and Blood Institute (NHLBI) increased its participation in the LRP by adding the Health Disparities Research Program to Clinical Research and Pediatric Research Programs. Objective: Before these substantive changes took effect, we sought to determine the impact of the NHLBI's participation in the LRP program on retention of scientists in the biomedical research workforce over the past 20 years. Methods: NHLBI LRP applicant cohorts from 2003 and 2008 were carefully examined with a 10-year follow-up period to measure the impact of applying for and obtaining NIH LRP funding on subsequent K- and R-level application and award rates, publication number, and average relative citation ratio as metrics to assess recruitment and retention of scientists in the biomedical research workforce. Results: Obtaining the LRP award was strongly associated with increased submission of and success in obtaining K- and RPG-grant funding and publications for both the 2003 and 2008 NHLBI LRP cohorts. An analysis of subgroups in the 2008 LRP cohort without prior F, K, or RPG funding revealed a consistently strong association between obtaining an LRP award and subsequent K- or RPG-award submission and success as well as potential synergy between obtaining an LRP award and participation on a T grant toward subsequent K- or RPG-award success rates. Conclusion: The LRP award appears to enhance retention in the biomedical research workforce when measured using metrics of grant application and award rates as well as research publications over a 10-year period.

The National Heart, Lung, and Blood Institute (NHLBI) AIDS Program's goal is to provide direction and support for research and training programs in areas of HIV-related heart, lung, blood, and sleep (HLBS) diseases. To better define NHLBI current HIV-related scientific priorities and with the goal of identifying new scientific priorities and gaps in HIV-related HLBS research, a wide group of investigators gathered for a scientific NHLBI HIV Working Group on December 14–15, 2015, in Bethesda, MD. The core objectives of the Working Group included discussions on: (1) HIV-related HLBS comorbidities in the antiretroviral era; (2) HIV cure; (3) HIV prevention; and (4) mechanisms to implement new scientific discoveries in an efficient and timely manner so as to have the most impact on people living with HIV. The 2015 Working Group represented an opportunity for the NHLBI to obtain expert advice on HIV/AIDS scientific priorities and approaches over the next decade.

Study of the human lung microbiome in the context of pulmonary health and disease is an area of emerging research interest that is being driven by several contributing factors. These factors include increased recognition of the diversity of human-associated microbiota, their roles in health and in diseases associated with chronic inflammation, and advancements in technologies and tools that have facilitated such discoveries about the microbiota in organ systems outside of the lung. Therefore, the overarching goals of lung microbiome research are: to identify and characterize microbial populations associated with the respiratory tract and lungs; to understand their roles in lung health and disease; and, we hope, to allow the development of improved approaches for diagnosing and treating chronic respiratory diseases in which the microbiome has a role. Recent studies of the lung microbiome have yielded a number of interesting findings but also highlighted questions and challenges for researchers and clinicians. In December 2011, the National Heart, Lung, and Blood Institute convened a workshop to identify key issues and areas for further attention or development to advance research on the lung microbiome. Current knowledge and the state of research on the lung and related areas of human microbiome investigation were reviewed and discussed.

The pulmonary physician-scientist has a special niche to generate basic research findings and apply them to a clinical disease and perhaps impact its medical care. The availability of new high throughput-based scientific technologies in the "omics era" has made this an opportune time for physician scientists to prepare and embark on an academic career in respiratory disease research. However, maintaining an adequate flow through the research pipeline of physician-scientist investigators studying respiratory system diseases is currently a challenge. There may not be a sufficient workforce emerging to capitalize on current research opportunities. The National Heart, Lung, and Blood Institute (NHLBI) organized a workshop to assess ways to attract and properly train advanced fellows to pursue research careers in adult and pediatric lung diseases. Participants included representatives from the various pulmonary training programs, respiratory-related professional societies, and NHLBI staff. Deliberation centered on present barriers that might affect interest in pursuing research training, devising better incentives to attract more trainees, and how current research support offered by the NHLBI and the Professional Societies (in partnership with Industry and Patient Support groups) might be better coordinated and optimized to ensure a continued pipeline of pulmonary investigators. Major recommendations offered are: (1) Attract trainees to pulmonary/critical care medicine-based research careers by increasing research exposure and opportunities for high school, college, and medical students. (2) Increase awareness of the outstanding physician-scientist role models in the lung community for trainees. (3) Facilitate mechanisms by which the lung community (NHLBI, professional societies, and partners) can better support and bridge senior fellows as they transition from Institutional Training Grants (T32) to Career Series (K) awards in their early faculty career development.

New technologies have made this an opportune time to prepare and embark on an academic career in respiratory disease research. The pulmonary physician-scientist has a special advantage to take basic research findings to the patient's illness and impact medical care. But is there a sufficient work force emerging to capitalize on current research opportunities? The aim of this study was to analyze the present workforce of potential clinical investigators available by reviewing the mechanisms of training support as provided by the National Heart Lung and Blood Institute (NHLBI) and by the professional pulmonary societies, including their patient advocacy groups and pharmaceutical partners, and by discussing how support for research training might be improved for advanced clinical fellows. Of the approximately 500 fellows/year in a final training year in Pulmonary/Critical Care Medicine and related programs, about one third are involved mainly in supervised research and of whom about two thirds plan to continue fellowship training for an additional year or more (approximately 100-120 trainees). It seems especially important to encourage his particular group who are planning to extend fellowship for research training. Both the NHLBI and the professional pulmonary societies and their partners provide support for advanced fellowship trainees, but resources are limited. To insure that enough well-trained new clinical investigators will be available to conduct future pulmonary research, funding support and other career inducements should be discussed collectively by the NHLBI and the professional pulmonary societies for the purpose of optimizing support for advanced fellowship trainees.

Human herpesvirus 8 (HHV-8) is a recently discovered virus that is highly associated with Kaposi's sarcoma (KS) and AIDS-associated body cavity lymphomas, although it is also found in some normal individuals. HHV-8 is related by nucleotide sequence homology to herpesvirus saimiri (HVS), which causes T cell lymphomas in some New World monkeys, and to Epstein–Barr virus (EBV), a human herpesvirus linked etiologically with Burkitt's lymphoma and nasopharyngeal carcinoma. We report that, like HVS but unlike EBV, HHV-8 contains a gene (ORF74) with significant sequence homology to the high-affinity IL-8 receptor, a member of the α (CXC) chemokine receptor family of transmembrane G protein-coupled receptors. We also show by reverse transcription PCR that the chemokine receptor-related HHV-8 gene is detectable in some RNA samples from KS tissue, and that its expression varies independently from that of ORF26, a minor capsid protein. The presence of a potential chemokine receptor in HHV-8 and its expression in KS tissue suggests that it may be important in the regulation of viral gene expression and may play a role in the etiology of KS and AIDS-related body cavity lymphomas.

In the present study the requirements for in vitro infection of antigen-specific CD8+ cytotoxic T lymphocytes (CTL) with human immunodeficiency virus –1(HIV-1) were investigated. CD3+CD8+CD4− HIV-1 nef-specific CTL become infected with HIV-1 after short-term co-culture with HLA-matched HIV-1-infected CD20+ B lymphoblastoid cells (B-LCL) which are specifically killed. Similar results were observed with an allospecific CD8+ CTL population. In addition, co-culture experiments showed that once infected with HIV-1, these CD8+ CTL could spread the infection further to uninfected CD4+ lymphocytes. In contrast, CD8+ CTL did not become infected with HIV-1 when co-cultured with HLA-mismatched HIV-1-infected B-LCL which are not killed. These observations in vitro could have relevance in peripheral lymphoid organs contributing to the progressive decrease of HIV-specific CD8+ CTL activity that is associated with the progression to AIDS.

To test the hypothesis that β-chemokine levels may be relevant to the control of HIVin vivo, we compared RANTES, MIP-1α, and MIP-1β production from purified CD8+T cells from 81 HIV-infected subjects and from 28 uninfected donors. Asymptomatic HIV+subjects produced significantly higher levels of MIP-1α and MIP-1β, but not RANTES, than uninfected donors or patients that progressed to AIDS. In contrast, β chemokines in plasma were either nondetectable or showed no correlation with clinical status. The high β-chemokine-mediated anti-HIV activity was against the macrophage tropic isolate HIV-1BAL, with no demonstrable effect on the replication of the T-cell tropic HIV-1IIIB. These findings suggest that constitutive β-chemokine production may play an important role in the outcome of HIV-1 infection.

T cell activation through the T cell receptor is necessary to achieve a specific and effective immune response. We report here that stimulation of CD8+T cells through the T cell receptor complex leads tode novoexpression of the CD4 antigen on the cell surface that results in susceptibility of CD8+T cells to HIV infection. In addition, activation of peripheral blood mononuclear cells from HIV-infected individuals results in the appearance of double-positive CD4+/CD8+T cells, which become infected by endogenous HIV. HIV DNA sequences could be detected in uncultured and sorted mature CD3+CD8+T cells from HIV+individuals. These results suggest a new mechanism by which HIV could attack the immune system and may help to explain the CD8+T cell defects in AIDS patients.

Basic fibroblast growth factor (bFGF) and human immunodeficiency virus type 1 (HIV-1) Tat protein synergize in inducing angiogenic Kaposi's sarcoma-like lesions in mice. Synergy is due to Tat, which enhances endothelial cell growth and type-IV collagenase expression in response to bFGF mimicking extracellular matrix proteins. The bFGF, extracellular Tat and Tat receptors are present in HIV-1-associated KS, which may explain the higher frequency and aggressiveness of this form compared to classical Kaposi's sarcoma where only bFGF is present.

Human T-cell leukemia-lymphoma virus (HTLV) is the first unequivocal human retrovirus. Seroepidemiological and virus isolation studies indicate that HTLV is etiologically associated with a subtype of adult T-cell malignancy. We have molecularly cloned approximately 1 kilobase of sequences derived from the 5' and 3' termini of the HTLV genome. Use of these clones as probes allowed isolation of a 9.8-kilobase EcoRI fragment from a genomic DNA library of an HTLV-infected neoplastic T-cell line (CR). Analysis of this clone revealed the presence of cellular sequences flanking approximately 5 kilobases of viral sequences including one long terminal repeat sequence. The 5' and 3' clones, as well as subclones derived from different regions of the genomic clone, were used as probes to compare integrated proviruses and viral RNA expression in different HLTV-infected neoplastic T cell lines. The results indicate that the infected cells are of clonal origin with respect to the virus integration sites and they express multiple viral mRNA species including a 35S RNA.

Human T-cell leukaemia-lymphoma virus (HTLV) was first isolated in the United States from a patient with an aggressive form of cutaneous T-cell lymphoma (CTCL) and was later found associated with clusters of adult T-cell leukaemia-lymphomas (ATL) in various parts of the world, including Japan and the Caribbean. Leukaemic cells of the HTLV-positive patients seem to be clonal expansions of single infected cells since the provirus(es) are found at the same sites in a given patient. In avian leukosis virus-induced B-cell lymphomas, the provirus very frequently integrates at several discrete sites in a common domain near the cellular gene, c-myc, that it activates and it has been speculated that the same would hold true for other chronic leukaemia viruses. We report here that cultured cells from two US patients with CTCL and fresh leukaemia cells of a Japanese patient with ATL contained an HTLV provirus integrated at the same site. In addition, a cord blood T-lymphocyte cell line established by co-cultivation with one of the two HTLV-positive CTCL cell lines also contained HTLV provirus contiguous with the same flanking cellular sequences. Ten other HTLV-positive cell samples did not show integration of HTLV at this site, suggesting that there is more than one discrete site of HTLV integration in tumour cells.

Human T-cell leukaemia-lymphoma virus (HTLV) is an exogenous human retrovirus distinct from all known animal retroviruses. HTLV is closely linked to a subtype of adult T-cell malignancies and except for isolated cases, has not been found associated with any other form of leukaemia, lymphoma or other cancers (see refs 1, 2 for review). HTLV can be transmitted to cord blood T lymphocytes in vitro and the infected cells exhibit characteristics of transformed neoplastic T cells. We have recently cloned DNA sequences derived from approximately 1 kilobase (kb) of the 5' and 3' termini of the HTLV genome, as well as a 4-5-kb defective HTLV provirus flanked by cellular sequences. The availability of these probes has enabled us to carry out a limited survey of different fresh or cultured cells from patients of different lymphoid and myeloid malignancies for HTLV-related DNA sequences. The results presented here show that cells from all Japanese patients with adult T-cell leukaemia and several patients with various mature T-cell malignancies from elsewhere contained one or more copies of a highly conserved HTLV genome. The infected cells are of clonal origin. Fresh cells from 1 of the 10 myeloid leukaemic patients contained exogenous DNA sequences distantly related to HTLV.

Three full-length cDNA clones were obtained from cells infected with the simian immunodeficiency virus (SIV) isolated from captive macaques (SIVMAC). Nucleotide sequence analyses suggested that these represented mRNA for the SIV MAC genes tat, rev (formerly, art/trs), and nef (formerly, 3'orf). The putative tat-specific clone was active in trans-activation of the SIV MAC long terminal repeat in COS-1 and Jurkat cells. In contrast, the human immunodeficiency virus 1 long terminal repeat was significantly trans-activated only in the COS-1 cells. This suggests that trans-activation by the SIV tat gene is modulated by cell-specific factors. The structure of all of the clones suggested an mRNA splicing pattern more complex than that described for human immunodeficiency virus 1.

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened a Working Group on the Microbiome in Cardiovascular, Pulmonary and Hematologic Health and Diseases from June 25, 2014, to June 26, 2014. The Working Group’s central goal was to define what major microbiome research areas warranted additional study in the context of heart, lung, and blood (HLB) diseases. The Working Group identified studies of the human virome a key priority.