Search PubMed⌕ Search

Biomedical subjects

S Iyengar

Publications and source records attributed to S Iyengar.

At least 19 recordsLinked to original sources
PubMed2006

A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain.

BACKGROUND: Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord. OBJECTIVE: To assess the efficacy of duloxetine, a dual reuptake inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP). METHODS: In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed. RESULTS: Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient's Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered. CONCLUSIONS: This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.

Acetaminophen↗
PubMed2005

Identification of a high-affinity binding site involved in the transport of endocannabinoids.

Phytocannabinoids, such as the principal bioactive component of marijuana, delta9-tetrahydrocannabinol, have been used for thousands of years for medical and recreational purposes. delta9-Tetrahydrocannabinol and endogenous cannabinoids (e.g., anandamide) initiate their agonist properties by stimulating the cannabinoid family of G protein-coupled receptors (CB1 and CB2). The biosynthesis and physiology of anandamide is well understood, but its mechanism of uptake (resulting in signal termination by fatty acid amide hydrolase) has been elusive. Mounting evidence points to the existence of a specific anandamide transport protein; however, no direct evidence for this protein has been provided. Here, we use a potent, competitive small molecule inhibitor of anandamide uptake (LY2318912, IC50 7.27 +/- 0.510 nM) to identify a high-affinity, saturable anandamide transporter binding site (LY2318912; K(d) = 7.62 +/- 1.18 nM, B(max) = 31.6 +/- 1.80 fmol/mg protein) that is distinct from fatty acid amide hydrolase. Systemic administration of the inhibitor into rodents elevates anandamide levels 5-fold in the brain and demonstrates efficacy in the formalin paw-licking model of persistent pain with no obvious adverse effects on motor function. Identification of the anandamide transporter binding site resolves a missing mechanistic link in endocannabinoid signaling, and in vivo results suggest that endocannabinoid transporter antagonists may provide a strategy for positive modulation of cannabinoid receptors.

Animals↗
PubMed2004

The effect of a kainate GluR5 receptor antagonist on responses of spinothalamic tract neurons in a model of peripheral neuropathy in primates.

The responses of antidromically identified spinothalamic tract (STT) neurons to mechanical and thermal stimuli were compared in anesthetized normal and neuropathic monkeys before and after administration of a GluR5 kainate receptor antagonist (LY382884) into the spinal cord dorsal horn through a microdialysis fiber. Peripheral neuropathy was induced by tight ligation of the L7 spinal nerve 13-15 days prior to the experiment. STT neurons recorded in the animals with neuropathy showed increased responsiveness to weak mechanical stimuli and to heating and cooling of the skin compared to STT cells in normal animals. In both normal and the neuropathic monkeys the responses of the STT neurons to mechanical and thermal stimuli were attenuated by LY382884 application in a concentration-dependent manner. Intraspinal application of LY382884 in the neuropathic animals led to a potent reduction of those responses of the STT neurons that were aggravated by the peripheral neuropathy (weak mechanical, heat and innocuous cooling stimuli). These results suggest that kainate receptors are involved in synaptic activation of STT cells in the normal state and may also play an important role in pathological pain states such as peripheral neuropathy in primates. Kainate receptor antagonists could thus be useful for the treatment of certain forms of allodynia and hyperalgesia.

Animals↗
PubMed2001

Identification of halogen atoms in scanning tunneling microscopy images of substituted phenyl octadecyl ethers.

A homologous series of para-substituted phenyl octadecyl ethers (X-POEs, where X = H, Cl, Br, I) was prepared using the Williamson ether synthesis and characterized by 1H NMR and GC/MS. Scanning tunneling microscopy images acquired from these ethers revealed a bias-dependent contrast corresponding to electron density contours of various X-POE molecular orbitals. Images reflecting the electron density contour of the highest occupied molecular orbital exhibited four bright spots--one for the halogen atom, two representing the pair of lobes of the phenyl ring, and one for the oxygen/alpha-carbon atoms. For each X-POE, the intensities (Zmax) of the spots for the halogen atom and the lobe of the phenyl ring closest to the halogen were measured and their ratio was calculated (Cl-POE 0.49 +/- 0.06; Br-POE 0.59 +/- 0.06; I-POE 0.75 +/- 0.07). Analysis of variance at the 95% confidence level revealed that the intensity ratios were consistent from molecule to molecule, image to image, and day to day. According to the Student t-test, the average Zmax ratios for Cl-POE, Br-POE, and I-POE are different at the 95% confidence level. In addition, they follow a trend that corresponds favorably with that of the atomic radii of the halogens. The probability of classifying a single X-POE molecule as Cl-POE, Br-POE, or I-POE is variable and depends on the magnitude of the Zmax ratio.

Journal Article↗
PubMed2001

Saturable transport of the neurokinin-1 non-peptide antagonist LY303870 across the rat blood-brain barrier after intravenous administration.

LY303870 (LY) is a non-peptide neurokinin-1 receptor antagonist that has effects on the brain after peripheral administration. We determined whether LY given by intravenous (iv) injection can cross the blood-brain barrier (BBB). Multiple-time regression analysis showed the unidirectional influx rate (Ki) from blood to brain for LY labeled with tritium to be 6.41+/-0.85 microl/g-min and influx was inhibited by unlabeled LY. HPLC and mass spectrometry showed LY was stable in blood and brain. LY reached a brain/serum ratio of 190+/-12 microl/g with about 0.07% of the injected dose entering each gram of brain. These results show that LY is transported across the BBB from serum into brain by a saturable system.

Animals↗
PubMed2001

Corticotropin-releasing factor (CRF) or CRF binding-protein ligand inhibitor administration suppresses food intake in mice and elevates body temperature in rats.

Corticotropin-releasing factor (CRF) receptor agonist and CRF binding-protein (CRF-BP) ligand inhibitor peptides both activate CRF systems but exert very distinct functional profiles in animal models of arousal, energy balance and emotionality. The present studies were designed to extend the dissimilar efficacy profiles of central administration of a CRF agonist, r/h CRF(1-41), versus a CRF-BP ligand inhibitor, r/h CRF(6-33), into mouse and rat models of energy balance in order to further explore in vivo efficacy of these ligands in two separate animal species. In CD-1 mice, food intake was significantly attenuated 3 h after acute administration of CRF(1-41) (0.007-0.2 nmol), but not CRF(6-33). In obese Ob/Ob mice, both CRF(1-41) (0.007-0.2 nmol) and CRF(6-33) (0.02-2.3 nmol) significantly attenuated basal feeding over 3 h following acute peptide administration. In rats, CRF(1-41) (1 nmol) and CRF(6-33) (1.5-7.7 nmol) infusion significantly increased rectal temperature. In studies employing a telemetry apparatus, core temperature was also increased by CRF(1-41) (1 nmol) and CRF(6-33) (1.5 nmol), whereas only CRF(1-41) increased locomotor activity and heart rate. These results suggest that CRF receptor agonist administration is capable of producing a global profile of negative energy balance by reducing food intake in mice and increasing energy expenditure in rats. In contrast, CRF-BP ligand inhibitor administration appears to suppress food intake in a mouse strain selective manner and to elevate rectal and core temperature in rats without accompanying cardiovascular activation.

Amphetamine↗
PubMed2001

The effect of lumbar sympathectomy on increased tactile sensitivity in spinal nerve ligated rats.

The aim of this study was to investigate the reason for the contradictory results following surgical sympathectomy on increased tactile sensitivity in spinal nerve ligated rats. For this purpose, firstly the results of L5 spinal nerve ligation alone and both L5 and L6 (L5/6) spinal nerve ligation were compared in Sprague-Dawley rats. Secondly, the difference in tactile sensitivity between the plantar surface (the middle glabrous area on the foot pads of the hind paw) and on the toe (the proximal half of the third and fourth toe of the hind paw) after the spinal nerve injury was studied. Third, we divided the L5 spinal nerve ligated rats into two groups, (i.e. low and high threshold groups) based on the degree of tactile sensitivity and investigated the effect of surgical lumbar sympathectomy (L2-L5) on tactile sensitivity in both the plantar and toe areas. The results show that the tactile sensitivities of L5 spinal nerve ligated rats and L5/6 spinal nerve ligated rats were not different. However, tactile sensitivities of the plantar surface were less than those of toe area suggesting that the response from toe is a better indicator of neuropathic pain. Surgical sympathectomy reduced the response from only the toe area and only in the low threshold group. These results suggest that the reason for the contradictory results of surgical sympathectomy in spinal nerve ligation models is, at least in part, the difference in the degree of mechanical allodynia in each study.

Animals↗
PubMed2001

Succinylcholine pretreatment using gallamine or mivacurium during rapid sequence induction in children: a randomized, controlled study.

STUDY OBJECTIVE: To determine if pretreatment with either gallamine or mivacurium before succinylcholine in children is associated with reduction in fasciculations; postoperative myalgias; or serum levels of potassium, creatinine phosphokinase (CPK), and myoglobin. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room at a children's hospital. PATIENTS: 45 ASA physical status IE children, aged 3 to 15 years, scheduled for emergency surgery. INTERVENTIONS: The children received either normal saline 0.5 mL, mivacurium chloride 0.03 mg. kg(-1), or gallamine triethiodide 0.04 mg. kg(-1)2 minutes prior to rapid sequence induction (RSI) using thiopental sodium 5 mg. kg(-1), fentanyl 2 microg. kg(-1), and succinylcholine 2 mg. kg(-1). MEASUREMENTS: Serum potassium concentration (0, 3, 5, 7.5, and 15 min), myoglobin concentration (5 and 15 min), and CPK concentration (0 min and 24 hr). Fasciculation and myalgia were rated on a 0 to 3 score. MAIN RESULTS: There was no difference between groups for fasciculation (p = 0.87) or myalgia score (p = 0.52). The mivacurium group had significantly less increase in potassium at 5 minutes (0.45 vs. 0.0, p = 0.01), myoglobin at 5 minutes (56 vs. 2, p < 0.001), myoglobin at 15 minutes (128 vs. 2.5, p < 0.001), and CPK at 24 hours (399 vs. 138, p < 0.001) following succinylcholine when compared with normal saline. Additionally, we found a significant level of association (p < 0.001) between fasciculation and myoglobin levels and fasciculation and CPK levels (p < 0.001). Gallamine was not effective in reducing the increase of potassium, myoglobin, or CPK. However, the dose of gallamine used for pretreatment was 13 times less than the dose of mivacurium. CONCLUSIONS: Administration of mivacurium 0.03 mg. kg(-1) intravenously 2 minutes before administration of succinylcholine 2 mg. kg(-1) in children is effective in reducing the increase in serum potassium at 5 minutes, the increase in myoglobin at 5 minutes and 15 minutes, and the increase in CPK at 24 hours.

Adolescent↗
PubMed2001

Electrocardiographic prediction of abnormal genotype in congenital long QT syndrome: experience in 101 related family members.

INTRODUCTION: Previous studies showed that diagnosing congenital long QT syndrome (LQTS) is difficult due to variable penetrance and genetic heterogeneity, especially when subjects from multiple families with diverse mutations are combined. We hypothesized that a combination of clinical and ECG techniques could identify gene carriers within a single family with congenital LQTS. METHODS AND RESULTS: One hundred one genotyped members of a family with LQTS, including 26 carriers of a HERG mutation, underwent history and ECG analysis. Forty-eight family members also underwent exercise testing with QT and T wave alternans (TWA) analysis and 24-hour Holter monitoring with QT and heart rate variability analysis. A logistic regression model, which included age, gender, QTc, and QTc by age, provided the best prediction of gene carrier status, although there was substantial overlap (78%) of QTc among subjects with and without the mutation. QTc was not helpful as a discriminator in children < or = 13 years. TWA (observed infrequently) did not add significantly to the model's ability to predict abnormal genotype. CONCLUSION: Even in this homogeneous LQTS population, the phenotype was so variable that clinical and detailed ECG analyses did not permit an accurate diagnosis of gene carrier status, especially in children. Sustained microvolt TWA was a specific (100%) but insensitive (18%) marker for LQTS. Its ability to predict risk of arrhythmia in this population remains to be determined. Genetic testing serves an essential role in screening for carriers of LQTS.

Adolescent↗
PubMed2001

Pharmacotherapy of malignant astrocytomas of children and adults: current strategies and future trends.

This article reviews the conceptual progression in the pharmacological therapy of malignant astrocytoma (MA) over the past decade, and its future trends. It is a selective rather than an exhaustive inventory of literature citations. The experience of the Brain Tumour Cooperative Group (BTCG) and earlier phase III trials are summarised to place subsequent phase II and I studies of single and combination agent chemotherapy in perspective. The BTCG experience of the 1970s to 1980s may be summarised to indicate that external beam radiotherapy (EBRT) is therapeutic, although not curative, and not further improved upon by altering fractionation schedules, or the addition of radioenhancers. Whole brain and reduced whole brain EBRT with focal boost were comparable regimens. Nitrosourea-based, adjuvant chemotherapy provided a modest improvement in survival among adult patients, which was comparable with that of other single drugs or multidrug regimes. The multiagent schedules, however, had a correspondingly higher toxicity rate. Intra-arterial administration was associated with significant risk, which conferred no therapeutic advantage. The trend of the past decade has been towards multiagent chemotherapy although its benefit cannot be predicted from the classic prognostic factors. Published experience with investigational trials utilising myeloablative chemotherapy with autologous bone marrow or peripheral blood stem cell haemopoietic support, drug delivery enhancement methods and radiosensitisers is critically reviewed. None of these approaches have achieved wide-spread acceptance in the treatment of adult patients with MA. Greater attention is placed on recent 'chemoradiotherapy' trials, which attempt to integrate and maximise the cytoreductive potential of both modalities. This approach holds promise as an effective means to delay or overcome the evolution of tumour resistance, which is probably one of the dominant determinants of prognosis. However, the efficacy of this approach remains unproven. New chemotherapeutic agents as well as biological response modifiers, protein kinase inhibitors, angiogenesis inhibitors and gene therapy are also discussed; their role in the therapeutic armamentarium has not been defined.

Adult↗
PubMed2001

The molecular genetics of therapeutic resistance in malignant astrocytomas.

The adverse prognosis associated with malignant astrocytomas (MA) is due in part to the development of resistance by the tumor to chemo- and radiotherapy-induced cytotoxic damage. The mechanisms of resistance are poorly understood but function at the level of the endothelial cell, the blood-brain barrier and the neoplastic cell itself. The classic examples of drug resistance proteins, such as the p-glycoprotein/multidrug resistance protein 1, have been identified within MA biopsy specimens. However, it is questionable to what degree, if at all, these proteins contribute directly to the evolution and prognosis of the MA. Surprisingly, there are specific genes, not traditionally associated with resistance, which appear increasingly relevant to both tumor progression and insensitivity to cytotoxic damage. These genes are involved in cell cycle regulation, and include the retinoblastoma susceptibility gene (Rb), the tumor suppressor gene p53, as well as those encoding the cyclins, their kinases and inhibitors. The interaction between the products of these genes and intratumoral environmental factors appears to involve a dynamic and prognostically adverse selection process. It is from this perspective that the mechanism(s) of hypoxic-ischaemic selection for resistance and its therapeutic repercussions will be analyzed.

Animals↗
PubMed2000

Clinical outcome after short-term psychotherapy for adolescents with major depressive disorder.

BACKGROUND: Cognitive behavioral therapy has been shown to be more efficacious than alternative psychosocial interventions for the acute treatment of adolescents with major depressive disorder. However, the long-term impact of brief psychosocial interventions on the course of adolescent depression is not well established. METHODS: One hundred seven adolescents with major depressive disorder randomly assigned to 12 to 16 weeks of cognitive behavioral therapy, systemic behavioral family therapy, or nondirective supportive therapy were evaluated for 2 years after the psychotherapy trial to document the subsequent course and predictors of major depressive disorder. RESULTS: There were no long-term differential effects of the 3 psychotherapies. Most participants (80%) recovered (median time, 8.2 months from baseline), and 30% had a recurrence (median time, 4.2 months from recovery). Twenty-one percent were depressed during at least 80% of the follow-up period. Severity of depression (at baseline) and presence of self-reported parent-child conflict (at baseline and during the follow-up period) predicted lack of recovery, chronicity, and recurrence. Despite the similarity to clinically referred patients at baseline, patients recruited via advertisement were less likely to experience a recurrence. CONCLUSIONS: There were no significant differences in long-term outcome among cognitive behavioral therapy, systematic behavioral family therapy, and nondirective supportive therapy. While most participants in this study eventually recovered, those with severe depression and self-perceived parent-child conflict are at greater risk for chronic depression and recurrences.

Adolescent↗
PubMed2000

Effect of acute and subchronic subcutaneous urocortin on blood pressure and food consumption in ob/ob mice.

Corticotropin-releasing factor and urocortin belong to a hypothalamic peptide family thought to be important in appetite regulation. The present study compared the appetite-suppressant effect of subcutaneous urocortin in obese mice to its cardiovascular effects. Acutely, urocortin (100 nmol/kg iv) reduced blood pressure and increased heart rate in urethane anesthetized nonobese mice; effects similar to those produced by subcutaneous urocortin (10 and 100 nmol/kg sc) in nonobese and ob/ob mice. Over this same dose range (10-100 nmol/kg sc), urocortin dramatically inhibited food consumption in the ob/ob mouse. To determine if the acute hypotensive effect of urocortin (10 nmol/kg sc) in the ob/ob mouse persisted after repeated urocortin administration, animals were pretreated for 3 days with urocortin (10 nmol/kg sc) or vehicle. Following urocortin pretreatment, urocortin-induced hypotension was similar to the effect in vehicle pretreated mice. However, urocortin-induced appetite suppression was reduced following 3 days of pretreatment with urocortin (10 nmol/kg sc) to ob/ob mice. These data suggest that the hypotensive and appetite-suppressant effects of urocortin are mediated by different mechanisms and tolerance to the hypotension did not readily occur in obese animals.

Animals↗
PubMed2000

Phasor transform to extract glucose and ascorbic acid data in an amperometric sensor.

A method for separating the signals from glucose and ascorbic acid on a single recognition surface using an ac immittance technique is presented. It is proposed that each oxidation process can be represented by a unique vector based on psi and YO, and that the concentration of each analyte can be determined by monitoring the change in the admittance magnitude in the direction of the characteristic angle for that particular species. The total Faradaic admittance (YF,total) for all electroactive species present is given by a linear combination of the independent vectors from the different species. In the system tested, the analytes are glucose and ascorbic acid, the former being estimated via the measurand, hydrogen peroxide. Thus, one of the electroactive species (hydrogen peroxide) is not a bulk solution species, but is 'generated' in the enzyme matrix. The admittance measurements from ascorbic acid and the enzyme-generated hydrogen peroxide showed the characteristic phase angles of each oxidation signal, allowing for good spatial resolution. The behaviour of each of these analytes is presented and calibration curves tested. Based on the calibration curves and the basis vectors, samples containing both glucose and ascorbic acid were measured by transforming the measured total admittance from the complex Cartesian space into 'analyte space', where the X-Y axes are given by the basis vectors ŷEGHP,GOD and ŷAA,GOD, respectively.

Ascorbic Acid↗
PubMed2000

Study of the analgesic effect of lanepitant in patients with osteoarthritis pain.

OBJECTIVE: Lanepitant selectively blocks substance P binding to the neurokinin-1 receptor, preventing neurogenic inflammation and pain transmission. Substance P is present in synovial fluid and in excess in cerebral spinal fluid. We investigated the effect of lanepitant on pain caused by osteoarthritis to evaluate the role of neurokinin-1 blockade. METHODS: Outpatients (n = 214) with moderate to severe lower-limb osteoarthritis pain were treated for 3 weeks in a parallel, randomized double-blind study with initial doses of 20, 60, 200, or 600 mg lanepitant, 375 mg naproxen, or placebo, followed by 10, 30, 100, or 300 mg lanepitant twice a day, 375 mg naproxen twice a day, or placebo twice a day in the multiple-dose period. Pain intensity, pain relief, patient global impression, and adjunctive analgesic use were compared across treatments. Safety was evaluated with adverse events, vital signs, and laboratory assessments. RESULTS: There was no statistically significant difference in efficacy or safety across treatments for the initial dose assessment. After 1 week of therapy, naproxen was statistically significantly (P < .05) better than placebo and lanepitant in reducing average pain. During the second and third weeks of therapy, patients receiving naproxen continued to have statistically significantly (P < .05) less pain than those receiving placebo or lanepitant despite using significantly less adjunctive analgesic medication. There were no statistically significant differences in rates of discontinuation across treatments. Lanepitant treatment was associated with diarrhea, whereas naproxen treatment was associated with gastric discomfort. There were no clinically relevant changes in vital signs or laboratory analytes for any of the treatments. CONCLUSION: Lanepitant was ineffective in relieving osteoarthritis pain, possibly because neurokinin-1 binding of substance P does not play a significant role in osteoarthritis pain or because lanepitant fails to adequately penetrate the blood-brain barrier to affect central pain perception.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Inaccuracy of clinical phenotyping parameters for hypertensive nephrosclerosis.

BACKGROUND: Multiple studies suggest that hypertension-induced end-stage renal disease (ESRD) is heritable. Identification of nephropathy susceptibility genes absolutely requires accurate phenotyping, but the clinical hypertensive nephrosclerosis (HN) phenotype is poorly characterized. We hypothesized that many patients with HN as the indicated cause of ESRD on the Health Care Financing Administration (HCFA) 2728 form, fail to satisfy stringent HN phenotyping criteria. METHODS: Since renal biopsy documentation of HN is uncommon, clinical parameters for HN phenotype were applied: family history of hypertension, left ventricular hypertrophy, proteinuria <0.5 g/day, and hypertension preceding renal dysfunction (Schlessinger et al., 1994) or urine protein:creatinine (prot:creat) ratio <2.0 and no evidence of other renal diseases (AASK Trial Group, 1997). RESULTS: ESRD patients (n=607, 73% African American, 25% Caucasian) were enrolled in a study to identify HN susceptibility genes. HN was the most common cause of ESRD according to HCFA 2728 forms (37% prevalence). Phenotyping of randomly selected patients with HN from the total cohort revealed that 4/100 subjects satisfied the Schlessinger criteria, and 28/91 African Americans met AASK criteria for HN. From these figures, the adjusted prevalence of HN was only 1.5-13.5%. Of patients that could not be phenotyped for HN, 14 were misdiagnosed, 14 had urine prot:creat >2.0, and insufficient data were available in the remainder. Four patients underwent renal biopsy, but histology from only one was consistent with HN. If the HN phenotype definitions are revised to exclude 'hypertension preceding renal dysfunction', or proteinuria limits, then 44/100 and 39/91 patients respectively satisfy clinical phenotyping parameters for HN. CONCLUSIONS: (i) We provide the strongest evidence to date that HN is less frequent in an ESRD population than commonly assumed if strict clinical criteria are used; many patients clinically diagnosed with HN may have undetected, treatable renal disease from other causes; (ii) relaxing HN phenotype criteria may erroneously include patients with glomerular diseases and secondary hypertension; (iii) reliance on HCFA 2728 diagnoses will confound identification of HN susceptibility genes; (iv) to attain adequate statistical power for genotype analysis, rigorous HN phenotyping will require screening an extremely large number of patients, which can be reasonably accomplished only in a multi-centre trial design.

Black People↗
PubMed2000

CD4-independent, CCR5-dependent simian immunodeficiency virus infection and chemotaxis of human cells.

Most simian immunodeficiency virus (SIV), human immunodeficiency virus type 2 (HIV-2), and HIV-1 infection of host peripheral blood mononuclear cells (PBMCs) is CD4 dependent. In some cases, X4 HIV-1 chemotaxis is CD4 independent, and cross-species transmission might be facilitated by CD4-independent entry, which has been demonstrated for some SIV strains in CD4(-) non-T cells. As expected for CCR5-dependent virus, SIV required CD4 on rhesus and pigtail macaque PBMCs for infection and chemotaxis. However, SIV induced the chemotaxis of human PBMCs in a CD4-independent manner. Furthermore, in contrast to the results of studies using transfected human cell lines, SIV did not require CD4 binding to productively infect primary human PBMCs. CD4-independent lymphocyte and macrophage infection may facilitate cross-species transmission, while reacquisition of CD4 dependence may confer a selective advantage for the virus within new host species.

Animals↗