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Abstract Background There are significant inequities between Māori (Indigenous people) and non-Māori in ageing outcomes. This study used a strengths-based approach based on the key cultural concept of mana motuhake (autonomy and self-actualisation) to develop a tuakana-teina (literally older sibling-younger sibling) peer education programme to assist kaumātua (elders) in addressing health and social needs. The purpose of this study was to test the impact on those receiving the programme. Three aims identify the impact on outcomes, resources received and the cost effectiveness of the programme. Methods Five Kaupapa Māori (research and services guided by Māori worldviews) iwi (tribe) and community providers implemented the project using a partnership approach. Tuakana (peer educators) had up to six conversations each with up to six teina (peer learners) and shared information related to social and health services. A pre- and post-test, clustered staggered design was the research design. Participants completed a baseline and post-programme assessment of health and mana motuhake measures consistent with Māori worldviews. Open-ended questions on the assessments, five focus groups, and four individual interviews were used for qualitative evaluation. Findings A total of 113 kaumātua were recruited, and 86 completed the programme. The analysis revealed improvements in health-related quality of life, needing more help with daily tasks, life satisfaction, paying bills and housing problems. Qualitative results supported impacts of the programme on mana motuhake and hauora (holistic health) through providing intangible and tangible resources. Cost-effectiveness analysis showed that the intervention is cost effective, with a cost per QALY of less than the conventional threshold of three times GDP per capita. Conclusions A culturally-resonant, strengths-based programme developed through a participatory approach can significantly improve health and social outcomes in a cost-effective way. Trial Registry Clinical trial registry: Trial registration: (ACTRN12620000316909). Prospectively registered 06/03/2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379302&isClinicalTrial=False .

BackgroundThe study offers baseline data for a strengths-based approach emphasizing intergenerational cultural knowledge exchange and physical activity developed through a partnership with kaumātua (Māori elders) and kaumātua service providers. The study aims to identify the baseline characteristics, along with correlates of five key outcomes.MethodsThe study design is a cross-sectional survey. A total of 75 kaumātua from six providers completed two physical functioning tests and a survey that included dependent variables based in a holistic model of health: health-related quality of life (HRQOL), self-rated health, spirituality, life satisfaction, and loneliness.ResultsThe findings indicate that there was good reliability and moderate scores on most variables. Specific correlates included the following: (a) HRQOL: emotional support (β = 0.31), and frequent interaction with a co-participant (β = 0.25); (b) self-rated health: frequency of moderate exercise (β = 0.32) and sense of purpose (β = 0.27); (c) spirituality: sense of purpose (β = 0.46), not needing additional help with daily tasks (β = 0.28), and level of confidence with cultural practices (β = 0.20); (d) life satisfaction: sense of purpose (β = 0.57), frequency of interaction with a co-participant (β = −0.30), emotional support (β = 0.25), and quality of relationship with a co-participant (β = 0.16); and (e) lower loneliness: emotional support (β = 0.27), enjoyment interacting with a co-participant (β = 0.25), sense of purpose (β = 0.24), not needing additional help with daily tasks (β = 0.28), and frequency of moderate exercise (β = 0.18).ConclusionThis study provides the baseline scores and correlates of important social and health outcomes for the He Huarahi Tautoko (Avenue of Support) programme, a strengths-based approach for enhancing cultural connection and physical activity.

Abstract Background Health inequities experienced by kaumātua (older Māori) in Aotearoa, New Zealand, are well documented. Examples of translating and adapting research into practice that identifies ways to help address such inequities are less evident. The study used the He Pikinga Waiora (HPW) implementation framework and the Consolidated Framework for Implementation Research (CFIR) to explore promising co-design and implementation practices in translating an evidence-based peer-education programme for older Māori to new communities. Methods The study was grounded in an Indigenous methodology (Kaupapa Māori) and a participatory research approach. Data were collected from research documentation, community meeting and briefing notes, and interviews with community researchers. Results The data analysis resulted in several key promising practices: Kaumātua mana motuhake (kaumātua independence and autonomy) where community researchers centred the needs of kaumātua in co-designing the programme with researchers; Whanaungatanga (relationships and connectedness) which illustrated how community researchers’ existing and emerging relationships with kaumātua, research partners, and each other facilitated the implementation process; and Whakaoti Rapanga (problem-solving) which centred on the joint problem-solving undertaken by the community and university researchers, particularly around safety issues. These results illustrate content, process, and relationship issues associated with implementation effectiveness. Conclusions This study showed that relational factors are central to the co-design process and also offers an example of a braided river, or He Awa Whiria, approach to implementation. The study offers a valuable case study in how to translate, adapt, and implement a research-based health programme to Indigenous community settings through co-design processes. Trial registration The project was registered on 6 March 2020 with the Australia New Zealand Clinical Trial Registry: ACTRN12620000316909 . Prospectively registered.

Abstract Background The Aotearoa New Zealand population is ageing accompanied by health and social challenges including significant inequities that exist between Māori and non-Māori around poor ageing and health. Although historically kaumātua (elder Māori) faced a dominant society that failed to realise their full potential as they age, Māori culture has remained steadfast in upholding elders as cultural/community anchors. Yet, many of today’s kaumātua have experienced ‘cultural dissonance’ as the result of a hegemonic dominant culture subjugating an Indigenous culture, leading to generations of Indigenous peoples compelled or forced to dissociate with their culture. The present research project, Kaumātua Mana Motuhake Pōī (KMMP) comprises two interrelated projects that foreground dimensions of wellbeing within a holistic Te Ao Māori (Māori epistemology) view of wellbeing. Project 1 involves a tuakana-teina/peer educator model approach focused on increasing service access and utilisation to support kaumātua with the greatest health and social needs. Project 2 focuses on physical activity and cultural knowledge exchange (including te reo Māori--Māori language) through intergenerational models of learning. Methods Both projects have a consistent research design and common set of methods that coalesce around the emphasis on kaupapa kaumatua; research projects led by kaumātua and kaumātua providers that advance better life outcomes for kaumātua and their communities. The research design for each project is a mixed-methods, pre-test and two post-test, staggered design with 2–3 providers receiving the approach first and then 2–3 receiving it on a delayed basis. A pre-test (baseline) of all participants will be completed. The approach will then be implemented with the first providers. There will then be a follow-up data collection for all participants (post-test 1). The second providers will then implement the approach, which will be followed by a final data collection for all participants (post-test 2). Discussion Two specific outcomes are anticipated from this research; firstly, it is hoped that the research methodology provides a framework for how government agencies, researchers and relevant sector stakeholders can work with Māori communities. Secondly, the two individual projects will each produce a tangible approach that, it is anticipated, will be cost effective in enhancing kaumātua hauora and mana motuhake. Trial registration Australia New Zealand Clinical Trial Registry ( ACTRN12620000316909 ). Registered 6 March 2020.

Abstract Background Aotearoa/New Zealand has a population that is ageing and there are challenges to health and social outcomes related to related to key life transitions (e.g., retirement, change in health conditions, loss of spouse). Further, there are significant inequities between Māori (Indigenous people) and non-Māori in ageing outcomes. The purpose of this study was to test the impacts and cost effectiveness of a tuakana/teina (peer education) intervention on kaumātua (elders) receiving the intervention. This study was framed by a strengths-based approach based on the key cultural concept of mana motuhake (autonomy and self-actualisation). Methods This study was grounded in principles of Kaupapa Māori and community-based participatory research to bring together a diverse group of stakeholders to co-develop and co-evaluate the intervention. The intervention had tuakana (peer educators) having conversations with up to six teina (recipients) and providing information related to health and social services. The research design was a pre- and post-test, clustered staggered design. Participants completed a baseline assessment of health and mana motuhake measures consistent with Māori worldviews along with two follow-up assessments (one after the first intervention group completed its activities and a second after the second intervention group completed its activities). Additionally, five focus groups and open-ended questions on the assessments were used to provide qualitative evaluation. Findings A total of 180 kaumātua were recruited to the intervention with 121 completing it. The analysis revealed improvements over time in the expected direction on most of the variables. However, only three of the variables had statistically significant intervention effects: received support, tribal identity, and trouble paying bills. Qualitative results supported impacts of the intervention on mana motuhake, social connectedness, and tangible/information support related to services. Cost-effectiveness analysis showed that the intervention is cost effective, with a cost per QALY of less than the conventional threshold of three times gross domestic product per capita. Conclusions The findings support the relevancy and importance of kaumātua knowledge to create a strengths-based approach to improve health and social outcomes. This study demonstrates that a contextually based and culturally safe age-friendly environments can facilitate engagement and participation by kaumātua for kaumātua. Trial registry Australia New Zealand Clinical Trial Registry (ACTRN12617001396314); Date Registered: 3 October 2017 (retrospectively registered); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373733&isClinicalTrial=False

BackgroundKnowledge of the challenges unpaid caregivers faced providing care to older people during the COVID-19 pandemic is limited. Challenges may be especially pronounced for those experiencing inequitable access to health and social care. This participatory action research study, located in New Zealand, has four main objectives, (i) to understand the challenges and rewards associated with caregiving to older care recipients during the COVID-19 pandemic restrictions; (ii) to map and collate resources developed (or mobilised) by organisations during the pandemic; (iii) to co-produce policy recommendations, identify useful caregiver resources and practices, prioritise unmet needs (challenges); and, (iv) to use project results in knowledge translation, in order to improve caregivers access to resources, and raise the profile and recognition of caregivers contribution to society.Methods and analysisMāori, Pacific and rural-dwelling caregivers to 30 older care-recipients, and 30 representatives from organisations supporting caregivers in New Zealand will be interviewed. Combining data from the interviews and caregivers letters (from an archive of older people's pandemic experiences), framework analysis will be used to examine the interrelated systems of the human ecological model and the impact on caregiving experiences during the pandemic. Resources that service providers had created or used for caregivers and older people will be collated and categorised. Through co-production with caregivers and community partners we will produce three short films describing caregivers' pandemic experiences; identify a suite of resources for caregivers to use in future events requiring self-isolation, and in everyday life; and generate ideas to address unresolved issues.

Background: Māori kaumātua (elders) face stark health and social inequities compared to non-Māori New Zealanders. The tuakana-teina (older sibling-younger sibling) peer education programme is a strengths-based approach to enhance well-being and social connectedness. The purpose of this study is to present the baseline data from this programme and identify correlates of well-being outcomes.Method: Participants included 128 kaumātua who completed a self-report survey about health-related quality of life, spirituality, social connection and loneliness, life satisfaction, cultural identity and connection, elder abuse, health service utilisation and demographics.Findings: Multiple regression models illustrated the following correlates of outcomes: (a) self-rated health: needing more help with daily tasks (β = −0.36) and housing problems (β = –0.17); (b) health-related quality of life: needing more help with daily tasks (β = –0.31), housing problems (β = –0.21), and perceived autonomy (β = 0.19); (c) spiritual well-being: understanding of tikanga (cultural protocols) (β = 0.32) and perceived autonomy (β = 0.23); (d) life satisfaction: social support (β = 0.23), sense of purpose (β = 0.23), cultural identity (β = 0.24), trouble paying bills (β = –0.16), and housing problems (β = –0.16); (e) loneliness: elder abuse (β = 0.27), social support (β = –0.21), and missing pleasure of being with whānau (extended family) (β = 0.19).Conclusions: Key correlates for outcomes centred on social support, housing problems, cultural connection and perceived autonomy. These correlates are largely addressed through the programme where tuakana/peer educators provide support and links to social and health services to teina/peer recipients in need. This study illustrates needs and challenges for kaumātua, whilst the larger programme represents a strengths-based and culturally-centred approach to address health issues related to ageing in an Indigenous population.

Abstract Background The Aotearoa/New Zealand population is ageing and numerous studies demonstrate with this phenomenon comes increases in non-communicable diseases, injuries and healthcare costs among other issues. Further, significant inequities exist between Māori (Indigenous peoples of Aotearoa/New Zealand) and non-Māori around poor ageing and health. Most research addressing these issues is deficit oriented; however, the current research project takes a strengths-based approach that highlights the potential of kaumātua (elders) by asserting mana motuhake (autonomy, identity and self-actualisation). We believe that the esteem of elders in Māori culture signals transformative potential. Specifically, this project utilises a ‘tuakana-teina’ (older sibling/younger sibling) peer-educator model, where kaumātua work with other kaumātua in relation to health and wellbeing. The objectives of the project are (a) to develop the capacity of kaumātua as peer educators, whilst having positive impacts on their sense of purpose, health and wellbeing; and (b) to enhance the social and health outcomes for kaumātua receiving the intervention. Methods The research is grounded in principles of Kaupapa Māori and community-based participatory research, and brings together an Indigenous community of kaumātua, community health researchers, and academic researchers working with two advisory boards. The project intervention involves an orientation programme for tuakana peer educators for other kaumātua (teina). The research design is a pre- and post-test, clustered staggered design. All participants will complete a baseline assessment of health and wellbeing consistent with Māori worldviews (i.e., holistic model). The tuakana and teina participants will be divided into two groups with the first group completing the intervention during the first half of the project and the second group during the second half of the project. All participants will complete post-test assessments following both interventions allowing comparison of the two groups along with repeated measures over time. Discussion The findings will provide an evidence base for the importance and relevancy of kaumātua knowledge to create contextually based and culturally safe age-friendly environments that facilitate engagement and participation by kaumātua for kaumātua. If the model is effective, we will seek to facilitate the dissemination and scalability of the intervention. Trial registration Australia New Zealand Clinical Trial Registry (ACTRN12617001396314); Date Registered: 3 October 2017 (retrospectively registered).

Background: The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD.Methods: Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1).Results: NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001).Conclusions: In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity.Trial Registry: ClinicalTrials.gov; No.: NCT00874965; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Obstetric fistula, caused by traumatic delivery and patient lack of access to obstetric care, is an important public health concern in developing countries, particularly in Sub-Saharan Africa. This research focuses on the experience of women living with obstetric fistula in Burkina Faso as well as their reintegration into community after surgery., Methods: This project was funded by the Mères du Monde en Santé (MMS) Foundation and conducted in collaboration with the Boromo Hospital. A qualitative approach based on grounded theory and using the principles of participative action research (PAR) was used with semidirected interviews prior to surgery and follow-up interviews 1-2 years after surgery directly in the women's village of origin. Thirty-nine participants were recruited between 2012 and 2015., Results: The results point to circumstances leading to obstetric fistula development: poverty, gender inequality in terms of decision making, healthcare-system deficiencies, and lack of services for referral and treatment of this condition. Our results reinforce the knowledge about the social and psychological repercussions of fistula by exploring the concepts of gossips, shame and self-exclusion as powerful mechanisms of exclusion, but they also show that social support was conserved for several women through their journey with this disease. There was complete social rehabilitation within the community after surgery; however, persistent barriers in term of anxiety regarding obstetric future and economic insecurity were present., Conclusions: Early recruitment for surgery and prevention are the main objectives when attempting to reduce the impact of obstetric fistula and facilitate patient reintegration. Improvements in local and governmental public health policies are required.

Since hypoxia might contribute to the development of muscle atrophy, we wished to provide direct evidence linking hypoxia to muscle atrophy. By evaluating protein degradation and synthesis in hypoxic myotubes we found a significant reduction in total protein content. Using functional assays we observed protein degradation elevation in the first 24 h while synthesis was maintained during this period and then significantly decrease at 48 h. These results demonstrate a temporal regulation of protein homeostasis, whereby elevated protein degradation is followed by a reduction in synthesis. These results are comparable to the cellular adaptation seen during development of muscle atrophy.

Background: Antisense transcription in retroviruses has been suggested for both HIV-1 and HTLV-I, although the existence and coding potential of these transcripts remain controversial. Thorough characterization is required to demonstrate the existence of these transcripts and gain insight into their role in retrovirus biology., Results: This report provides the first complete characterization of an antisense retroviral transcript that encodes the previously described HTLV-I HBZ protein. In this study, we show that HBZ-encoding transcripts initiate in the 3' long terminal repeat (LTR) at several positions and consist of two alternatively spliced variants (SP1 and SP2). Expression of the most abundant HBZ spliced variant (SP1) could be detected in different HTLV-I-infected cell lines and importantly in cellular clones isolated from HTLV-I-infected patients. Polyadenylation of HBZ RNA occurred at a distance of 1450 nucleotides downstream of the HBZ stop codon in close proximity of a typical polyA signal. We have also determined that translation mostly initiates from the first exon located in the 3' LTR and that the HBZ isoform produced from the SP1 spliced variant demonstrated inhibition of Tax and c-Jun-dependent transcriptional activation., Conclusion: These results conclusively demonstrate the existence of antisense transcription in retroviruses, which likely plays a role in HTLV-I-associated pathogenesis through HBZ protein synthesis.

Similar to several other viruses, human T cell leukemia virus type I (HTLV-I) induces the formation of multinucleated giant cells (also known as syncytium) when amplified in tissue culture. These syncytia result from the fusion of infected cells with uninfected cells. Due to the intrinsic difficulty of infecting cells with cell-free HTLV-I virions, syncytium formation has become an important tool in the study of HTLV-I infection and transmission. Since most HTLV-I-based cell fusion assays rely on the use of non-T cells, the aim of this study was to optimize a new HTLV-I-induced cell fusion assay in which HTLV-I-infected T cell lines are co-cultured with T cells that have been transfected with an HTLV-I long terminal repeat (LTR) luciferase reporter construct. We demonstrate that co-culture of various HTLV-I-infected T cells with different transfected T cell lines resulted in induction of luciferase activity. Cell-to-cell contact and expression of the viral gp46 envelope protein was crucial for this induction while other cell surface proteins (including HSC70) did not have a significant effect. This quantitative assay was shown to be very sensitive. In this assay, the cell fusion-mediated activation of NF-kappaB and the HTLV-I LTR occurred through previously described Tax-dependent signaling pathways. This assay also showed that cell fusion could activate Tax-inducible cellular promoters. These results thus demonstrate that this new quantitative HTLV-I-dependent cell fusion assay is versatile, highly sensitive, and can provide an important tool to investigate cellular promoter activation and intrinsic signaling cascades that modulate cellular gene expression.

The enhancer region in the human immunodeficiency virus type 1 (HIV-1) 5'-long terminal repeat (LTR) is very important for viral transcription. This promoter sequence binds both nuclear factor-kappaB and NFAT, two important modulators of HIV-1 gene expression. Previous studies have indicated that the enhancer regions of the different HIV-1 clade LTRs differ in their number of NF-kappaB-binding sites. In this study, we have compared the activation potential of the different HIV-1 clade and HIV-2 LTRs and assessed their interaction with NFAT and NF-kappaB. In T-cell lines and primary CD4(+) T-cells, the results showed that the HIV-1 clade E LTR (with a single NF-kappaB-binding site) was the weakest LTR regardless of the tested activators, whereas the HIV-2 LTR was the most responsive LTR. The clade E enhancer region was also demonstrated to be the weakest enhancer region in transfection experiments with luciferase reporter-based vectors. Electrophoretic mobility shift assays with extracts from activated CD4(+) T-cells indicated that, although NF-kappaB and NFAT bound all enhancers, HIV-1 clade E and HIV-2 LTR enhancers were poor binding targets for these two factors. Weak NFAT binding to clade E enhancers was also confirmed using NFAT1-expressing 293T cells in competition experiments. We have also shown the absence of interaction of NF-kappaB or NFAT with the third NF-kappaB repeat present in clade C. However, the clade C enhancer bound NFAT more efficiently than all other enhancer regions tested. Our results hence demonstrate for the first time that differences in the binding of NF-kappaB and NFAT to the enhancer regions could be responsible for some of the observed variation in HIV-1 clade LTR activation, whereas HIV-2 LTR activation seems mostly independent of these interactions.

Human T-cell leukemia virus type I (HTLV-I) transcription generally depends on the ability of the viral Tax protein to bind the CREB transcription factor and form an active complex by recruiting CBP/p300 coactivators to the long terminal repeat (LTR). Studies have demonstrated that T-cell activating agents that stimulate CREB are potent inducers of HTLV-I transcription. Herein, we demonstrate that bpV[pic], a protein tyrosine phosphatase (PTP) inhibitor activates the HTLV-I LTR in the presence and absence of Tax expression. Optimal activation occurred at 8 h and was synergistic with forskolin or PGE(2). Infected cell lines and cells transfected with HTLV-I proviral DNA were equally responsive to the synergistic effect of bpV and forskolin on HTLV-I gene expression. Activation of the LTR by bpV[pic] was T-cell receptor-independent, but required ZAP70, calcineurin activity and functional calcium entry. Inhibition of the SHP-1 PTP was suggested to be important. Transfection experiments with a CREB dominant-negative mutant and with isolated TRE1- or CREB-responsive reporter constructs and treatment with the MDL-12,330A adenylate cyclase inhibitor all supported the involvement of a CREB/ATF family member in this bpV-dependent activation of the HTLV-I LTR, although CREB itself did not seem to be involved. Analysis of HTLV-I reporter constructs containing mutated CREB-binding sites also implied the involvement of another element in this activation. These results demonstrate for the first time a powerful effect of PTP inhibitors on HTLV-I LTR activity and suggest participation of both CREB-dependent and -independent pathways in this activation.

Infection with human T-cell leukemia virus type 1 (HTLV-1) is characterized by long latency periods, indicating that viral gene expression is under tight control. There is presently little information available regarding the nature of extracellular stimuli that can transactivate the regulatory elements of HTLV-1 (i.e., long terminal repeat [LTR]). To gain insight into the biological importance of externally induced activation pathways in virus gene expression, primary and established T cells were transfected with HTLV-1-based reporter gene vectors and then were treated with agents that cross-linked the T-cell receptor (TCR) or the costimulatory CD28 molecule with prostaglandin E(2) (PGE(2)). We demonstrated that a potent induction of HTLV-1 LTR-driven reporter gene activity was seen only when the three agents were used in combination. Interestingly, similar observations were made when using C91/PL, a cell line that carries integrated HTLV-1 proviral DNA. This TCR-CD28-PGE(2)-mediated increase in virus transcription was dependent on protein kinase A activation and induction of the cAMP response element binding protein. Experiments with a mutated reporter construct further revealed the importance of the Tax-responsive elements in the HTLV-1 LTR in the observed up regulation of virus gene expression when TCR/CD28 engagement was combined with PGE(2) treatment. The protein tyrosine kinases p56(lck) and the transmembrane tyrosine phosphatase CD45 were all found to be involved in TCR-CD28-PGE(2)-directed increase in HTLV-1 LTR activity. This study presents new information on the possible mechanisms underlying reactivation of this retrovirus.

Although protein tyrosine phosphatase (PTP) inhibitors used in combination with other stimuli can induce interleukin 2 (IL-2) production in T cells, a direct implication of nuclear factor of activated T cells (NFAT) has not yet been demonstrated. This study reports that exposure of leukemic T cells and human peripheral blood mononuclear cells to bis-peroxovanadium (bpV) PTP inhibitors markedly induce activation and nuclear translocation of NFAT. NFAT activation by bpV was inhibited by the immunosuppressive drugs FK506 and cyclosporin A, as well as by a specific peptide inhibitor of NFAT activation. Mobility shift assays showed specific induction of the NFAT1 member by bpV molecules. The bpV-mediated NFAT activation was observed to be important for the up-regulation of the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) and the IL-2 promoter; NFAT1 was demonstrated to be particularly important in bpV-dependent positive action on HIV-1 LTR transcription. The active participation of p56(lck), ZAP-70, p21(ras), and calcium in the bpV-mediated signaling cascade leading to NFAT activation was confirmed, using deficient cell lines and dominant-negative mutants. Finally, overexpression of wild-type SHP-1 resulted in a greatly diminished activation of NFAT by bpV, suggesting an involvement of SHP-1 in the regulation of NFAT activation. These data were confirmed by constitutive NFAT translocation observed in Jurkat cells stably expressing a dominant-negative version of SHP-1. The study proposes that PTP activity attenuates constitutive kinase activities that otherwise would lead to constant NFAT activation and that this activation is participating in HIV-1 LTR stimulation by PTP inhibition.