Factors secreted by human T lymphotropic virus type I (HTLV-I)-infected cells can enhance or inhibit replication of HIV-1 in HTLV-I-uninfected cells: implications for in vivo coinfection with HTLV-I and HIV-1.

It remains controversial whether human T lymphotropic virus type I (HTLV-I) coinfection leads to more rapid progression of human immunodeficiency virus (HIV) disease in dually infected individuals. To investigate whether HTLV-I infection of certain cells can modulate HIV-1 infection of surrounding cells, primary CD4(+) T cells were treated with cell-free supernatants from HTLV-I-infected MT-2 cell cultures. The primary CD4+ T cells became resistant to macrophage (M)-tropic HIV-1 but highly susceptible to T cell (T)-tropic HIV-1. The CC chemokines RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta in the MT-2 cell supernatants were identified as the major suppressive factors for M-tropic HIV-1 as well as the enhancers of T-tropic HIV-1 infection, whereas soluble Tax protein increased susceptibility to both M- and T-tropic HIV-1. The effect of Tax or CC chemokines on T-tropic HIV-1 was mediated, at least in part, by increasing HIV Env-mediated fusogenicity. Our data suggest that the net effect of HTLV-I coinfection in HIV-infected individuals favors the transition from M- to T-tropic HIV phenotype, which is generally indicative of progressive HIV disease.

Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1.

Microbial coinfections variably influence HIV-1 infection through immune activation or direct interaction of microorganisms with HIV-1 or its target cells. In this study, we investigated whether exposure of macrophages to bacterial products impacts the susceptibility of these cells to HIV-1 of different cellular tropisms. We demonstrate that () macrophages exposed to bacterial cell wall components such as lipopolysaccharide (LPS) (Gram-negative rods), lipoteichoic acid (Gram-positive cocci), and lipoarabinomannan (Mycobacteria) become highly susceptible to T cell (T)-tropic HIV-1 (which otherwise poorly replicate in macrophages) and variably susceptible to macrophage (M)-tropic HIV-1; () LPS-stimulated macrophages secrete a number of soluble factors (i.e., chemokines, interferon, and proinflammatory cytokines) that variably affect HIV infection of macrophages, depending on the virus phenotype in question; and () LPS-stimulated macrophages express CCR5 (a major coreceptor for M-tropic HIV-1) at lower levels and CXCR4 (a major coreceptor for T-tropic HIV-1) at higher levels compared with unstimulated macrophages. We hypothesize that a more favorable environment for T-tropic HIV-1 and a less favorable or even unfavorable environment for M-tropic HIV-1 secondary to exposure of macrophages to those bacterial products may accerelate a transition from M- to T-tropic viral phenotype, which is indicative of disease progression.

Clinical utility of negative contrast intravascular ultrasound to evaluate plaque morphology before and after coronary interventions.

Although intravascular ultrasound (IVUS) is used for evaluation of plaque volume and lumen size as well as detection of vessel wall structures after catheter-based interventions, differentiation between the lumen and plaque structures can be difficult. This study attempted to evaluate the efficacy of negative contrast IVUS imaging for assessment of vessel wall morphology after coronary interventions. IVUS studies were performed in 67 lesions in 66 patients before and after coronary interventions. After the baseline ultrasound imaging run, warm 5% glucose solution was injected manually through the guiding catheter into the coronary artery to washout blood from the lumen to avoid speckled reflections from red blood cells (negative contrast). Quantitative measurements were obtained and plaque morphology was assessed for the presence and extent of medial dissections and intimal flaps. There was no difference in each quantitative parameter between baseline images and negative contrast images. The vessel wall boundary was clearly delineated from the lumen, which was defined as effective negative contrast in 51 of 67 lesions (76%). The baseline images revealed plaque dissection in 9 lesions (18%) and an intimal flap in 13 lesions (25%). In addition, 4 dissections (8%) and 16 intimal flaps (31%) were visualized during the infusion of negative contrast. Additional treatment was performed in 4 lesions (8%) based on the images with negative contrast. Negative contrast IVUS was more sensitive in demonstrating a plaque fracture than were baseline images. This method is useful for enhancing the diagnostic capability of IVUS imaging and may influence the decision-making process during interventional procedures.

HTLV type I Tax activation of the CXCR4 promoter by association with nuclear respiratory factor 1.

Human T lymphotropic virus type I trans-activator Tax protein regulates expression of several cellular genes that are involved in cellular activation, proliferation, and transformation. Tax mediates its regulatory activity through interaction with cellular transcription factors such as members of the cAMP-responsive element-binding factors/ATF family or the NF-kappaB/Rel family. In this study we have demonstrated that Tax trans-activates the promoter for CXCR4, a coreceptor for T cell-tropic HIV-1 through its association with nuclear respiratory factor 1 (NRF1). The promoter region for CXCR4 contains an NRF1-binding site, which is crucial for basal and Tax-induced activity. Glutathione S-transferase (GST) pull-down experiments showed association of GST-Tax fusion protein with NRF1 in vitro. Expression of Tax, in addition to stimulation with phorbol myristate acetate and ionomycin, increased formation of the NRF1 complex in a gel-mobility shift assay, indicating that Tax association with NRF1 in vivo facilitates its DNA binding. HTLV-I Tax activation of CXCR4 may contribute to the rapid progression of HIV disease observed in certain coinfected individuals.

The reproducibility of intravascular ultrasound imaging in vitro.

To determine which factors may affect the image quality when an intravascular ultrasound catheter is used in vivo, the influence of blood, temperature change, and contrast media were evaluated. In addition, to confirm the reproducibility of intravascular ultrasound imaging to measure cross-sectional lumen area, intraobserver and interobserver variability were determined. The findings indicated that ultrasound images in blood are mildly attenuated, that changes from room temperature to body temperature do not have a significant impact on the image quality, that contrast media attenuates the image intensity in a dose-dependent manner, and that the intravascular ultrasound imaging catheter provides a reproducible method for measuring arterial lumen area with excellent intraobserver and interobserver correlation.

Disseminated cutaneous zoster and aseptic meningitis in a previously healthy patient.

A previously healthy, 37-year-old immunocompetent man presented with disseminated cutaneous zoster and aseptic meningitis. Varicella zoster virus DNA was recovered from the cerebrospinal fluid (CSF) by the polymerase chain reaction. Cytological evaluation of the CSF revealed 'reactive, highly atypical lymphocytosis'. The patient fully recovered after treatment with aciclovir.

Sudden appearance of coronary thrombus observed by angiography--a case report.

A sudden coronary thrombus formation was documented by chance during cardiac catheterization in a patient with postinfarction angina. The thrombus was successfully treated with intravenous urokinase and heparin infusions, and thereafter, coronary angioplasty was performed without any complication.

Intravascular ultrasonic imaging.

Because conventional imaging methods are inadequate for evaluating human coronary arteries in vivo, an intravascular ultrasonic imaging catheter was developed that allows the arterial wall to be studied in cross-section from within the artery. The catheter incorporates a mechanically rotating 20-MHz transducer, which is designed so that the ringdown occurs within the catheter and imaging is permitted up to the catheter's surface. The device rotates at 1800-rpm within a plastic sleeve and provides real-time cross-sectional images at 30 frames/sec. Preliminary experimental and clinical studies indicate that the intravascular ultrasonic imaging catheter could play a valuable role in providing preoperative information concerning arterial wall thickness and tissue characteristics, in distinguishing normal from diseased arterial wall structures during therapeutic intervention, and in assessing the results of intervention.

Emergence of Epstein-Barr virus-associated haemophagocytic syndrome upon treatment of systemic lupus erythematosus.

A 32-year-old female patient with systemic lupus erythematosus was admitted to our hospital with fever and cytopenia, and diagnosed as haemophagocytic syndrome (HPS) by bone marrow aspiration study showing haemophagocytosis. Since the serologic activity of lupus was not increased at that time and HPS was refractory to the conventional therapies, an additional aetiological factor was suspected. Real-time PCR analysis identified reactivation of Epstein-Barr virus (EBV). A combination therapy targetting EBV-associated HPS, consisting of intravenous administration of cyclosporine A as well as immunoglobulin with a high titre of anti-EBV antibody, significantly suppressed EBV viraemia and led to the remission of HPS until the time of writing.

A milk protein lactoferrin enhances human T cell leukemia virus type I and suppresses HIV-1 infection.

Human T cell leukemia virus type I (HTLV-I) and HIV-1, causative agents of adult T cell leukemia/lymphoma and AIDS, respectively, are transmitted vertically via breast milk. Here we demonstrate that lactoferrin, a milk protein that has a variety of antimicrobial and immunomodulatory activities, facilitates replication of HTLV-I in lymphocytes derived from asymptomatic HTLV-I carriers and transmission to cord blood lymphocytes in vitro. Transient expression assays revealed that lactoferrin can transactivate HTLV-I long terminal repeat promoter. In contrast, lactoferrin inhibits HIV-1 replication, at least in part, at the level of viral fusion/entry. These results suggest that lactoferrin may have different effects on vertical transmission of the two milk-borne retroviruses.

Class I-unrestricted noncytotoxic anti-HTLV-I activity of CD8(+) T cells.

Although it is widely believed that viral clearance is mediated principally by the destruction of infected cells by cytotoxic T cells, noncytolytic antiviral activity of CD8(+) T cells may play a role in preventing the progression to disease in infections with immunodeficiency viruses and hepatitis B virus. We demonstrate here that (1) replication of human T-lymphotropic virus type I (HTLV-I) is more readily detected from CD8(+) T-cell-depleted (CD8(-)) peripheral blood mononuclear cells (PBMCs) of healthy HTLV-I carriers than from unfractionated PBMCs, (2) cocultures of CD8(-) PBMCs with autologous or allogeneic CD8(+) T cells suppressed HTLV-I replication, and (3) CD8(+) T-cell anti-HTLV-I activity is not abrogated in trans-well cultures in which CD8(+) cells are separated from CD8(-) PBMCs by a permeable membrane filter. These results suggest that class I-unrestricted noncytolytic anti-HTLV-I activity is mediated, at least in part by a soluble factor(s), and may play a role in the pathogenesis of HTLV-I infection. (Blood. 2000;96:1994-1995)

In vitro induction of HIV-1 replication in resting CD4(+) T cells derived from individuals with undetectable plasma viremia upon stimulation with human T-cell leukemia virus type I.

Microbial coinfections have been associated with transient bursts of human immunodeficiency virus (HIV) viremia in patients. In this study we investigated whether human T-cell leukemia virus type I (HTLV-I), another human retrovirus that is prevalent among certain HIV-infected populations, can induce HIV-1 replication in patients who had been successfully treated with highly active antiretroviral therapy. We demonstrate that supernatants from HTLV-I-producing MT-2 cells can induce in vitro replication of HIV-1 from highly purified, resting CD4(+) T cells obtained from individuals with undetectable plasma viremia. Depletion of proinflammatory cytokines from the supernatants reduced, but did not abrogate, the ability to induce HIV-1 replication, indicating that other factors such as HTLV-I Tax or Env also have a role. The HTLV-I-mediated effect does not require productive infection: exposure to heat-inactivated HTLV-I virions, purified Tax protein, or HTLV-I Env glycoprotein also induced expression of HIV-1. Furthermore, we demonstrate that coculture of resting CD4(+) T cells with autologous CD8(+) T cells markedly inhibits the HTLV-I-induced virus replication. Our results suggest that coinfection with HTLV-I may induce viral replication in the latent viral reservoirs; however, CD8(+) T cells may play an important role in controlling the spread of virus upon microbial stimulation.