Biomedical subjects

C J Miller

Publications and source records attributed to C J Miller.

At least 19 recordsLinked to original sources

PubMed2001

Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses.

The purpose of this study was to determine whether rhesus monkeys of Chinese origin are suitable for studies of mucosal lentivirus transmission by comparing the relative ability of these animals and rhesus macaques of Indian origin to become infected by vaginal (IVAG) inoculation with SIVmac251. In addition, we sought to test the hypothesis that differences in viral load during the first few weeks after inoculation were due to the relative strength of the anti-SIV immune responses in the two populations of rhesus macaques. Significant difference was not observed between the number of Indian and Chinese origin monkeys that were infected after IVAG SIV inoculation in this study. For 8-9 weeks after infection there was considerable overlap in the range of viral loads among the Indian and Chinese animals and the variation among the Indian origin animals was greater than the variation among the Chinese origin monkeys. By 6 weeks postinfection, viral loads in SIV-infected Chinese origin monkeys tended to be at the lower end of the range of viral loads observed in SIV-infected Indian origin monkeys. The strength of the anti-SIV antibody response was also more variable in the Indian origin rhesus macaques, but at 6-8 weeks postinfection, Chinese and Indian origin rhesus macaques had similar titers of anti-SIV antibodies. Microsatellite allele frequencies differed between Chinese and Indian rhesus macaques; however, the majority of alleles present in Indian-origin animals were also found in Chinese macaques. Together these results show that host factors, other than geographic origin, determine the ability of a rhesus macaque to be infected after IVAG SIV exposure and that geographic origin does not predict the viral load of SIV-infected animals during the first 8-9 weeks after IVAG inoculation.

Animals↗

PubMed2001

Acoustic oscillations in the early universe and today.

During its first approximately 100,000 years, the universe was a fully ionized plasma with a tight coupling by Thompson scattering between the photons and matter. The trade-off between gravitational collapse and photon pressure causes acoustic oscillations in this primordial fluid. These oscillations will leave predictable imprints in the spectra of the cosmic microwave background and the present-day matter-density distribution. Recently, the BOOMERANG and MAXIMA teams announced the detection of these acoustic oscillations in the cosmic microwave background (observed at redshift approximately 1000). Here, we compare these CMB detections with the corresponding acoustic oscillations in the matter-density power spectrum (observed at redshift approximately 0.1). These consistent results, from two different cosmological epochs, provide further support for our standard Hot Big Bang model of the universe.

Journal Article↗

PubMed2001

The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques.

A number of studies have shown that the ovarian hormone cycle affects genital tract immunoglobulin (Ig) levels and T cell function in both humans and rhesus monkeys. We hypothesized that shifts in immune cell populations occurring in response to hormone cycles are involved in the observed changes in genital tract immunity. To test this hypothesis, we characterized the type, number, and distribution of immune cells in the cervicovaginal mucosa at different stages of the menstrual cycle. Tissues from 18 normal female rhesus macaques were studied by immunohistochemistry and computerized morphometric analysis. The number and distribution of CD1a+ Langerhans' cells, CD2+, CD3+, CD4+, and CD8+ T cells, CD20+ B cells, and surface Ig+ plasma cells did not change in samples collected at the different stages of the cycle. However, in no relation to the stage of the menstrual cycle, the number of Langerhans' cells and other immune cell types was different in the various regions of the cervicovaginal mucosa examined. In addition, variation in thickness of the ectocervical and vaginal epithelium during a normal menstrual cycle of rhesus macaques is not accompanied by changes in intraepithelial immune cell populations. We conclude that steroid hormones do not influence genital mucosal immunity by changing the number or distribution of immune cells in the lower reproductive tract.

Animals↗

PubMed2001

Which craft is best in bioinformatics?

'Silicon-based' biology has gathered momentum as the world-wide sequencing projects have made possible the investigation and comparative analysis of complete genomes. Central to the quest to elucidate and characterise the genes and gene products encoded within genomes are pivotal concepts concerning the processes of evolution, the mechanisms of protein folding, and, crucially, the manifestation of protein function. Our use of computers to model such concepts is limited by, and must be placed in the context of, the current limits of our understanding of these biological processes. It is important to recognise that we do not have a common understanding of what constitutes a gene; we cannot invariably say that a particular sequence or fold has arisen via divergence or convergence; we do not fully understand the rules of protein folding, so we cannot predict protein structure; and we cannot invariably diagnose protein function, given knowledge only of its sequence or structure in isolation. Accepting what we cannot do with computers plays an essential role in forming an appreciation of what we can do. Without this understanding, it is easy to be misled, as spurious arguments are often used to promote over-enthusiastic notions of what particular programs can achieve. There are valuable lessons to be learned here from the field of artificial intelligence, principal among which is the realisation that capturing and representing complex knowledge is time consuming, expensive and hard. If bioinformatics is to tackle biological complexity meaningfully, the road ahead must therefore be paved with caution, rigour and pragmatism.

Amino Acid Sequence↗

PubMed2001

The use of an objective structured clinical examination (OSCE) for formative and summative assessment in a general practice clinical attachment and its relationship to final medical school examination performance.

OBJECTIVES: To report the use of OSCEs for both formative and summative purposes within a general practice undergraduate clinical attachment and to compare student performance in the departmental OSCEs with that of their final medical school examinations. METHODS: Twenty-eight students rotated through the attachment and undertook pre- and post-attachment OSCEs of similar format but different content. Results were analysed to determine relationships between mean scores in the two OSCEs and student performance in their final medical school MBBS examinations. RESULTS: There was a marked improvement in all OSCE station scores. Pre-attachment scores for those stations measuring physical examination and problem-solving skills were unrelated to prior clinical experience. Post-attachment OSCE mean scores were significantly correlated with final examination OSCE and total mean scores. CONCLUSION: The general practice attachment appears to upgrade those clinical skills measured by the pre- and post-attachment OSCE, however, there was no control group of students. Problem-solving and focused physical examination skills need to be targeted by all undergraduate clinical departments. The department's post-attachment OSCE and total assessment results are predictors of final examination OSCE and total results. The use of pre- and post-attachment OSCEs facilitates both students' formative learning processes and the department's evaluation of its educational programme.

Clinical Competence↗

PubMed2001

Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix.

Unraveling the molecular basis of inherited disorders of epithelial fragility has led to understanding of the complex structure and function of keratin intermediate filaments. Keratins are organized as a central alpha-helical rod domain flanked by nonhelical, variable end domains. Pathogenic mutations in 19 different keratin genes have been identified in sequences corresponding to conserved regions at the beginning and end of the rod. These areas have been recognized as zones of overlap between aligned keratin proteins and are thought to be crucial for proper assembly of keratin intermediate filaments. Consequently, all keratin disorders of skin, hair, nail, and mucous membranes caused by mutations in rod domain sequences are characterized by perinuclear clumping of fragmented keratin intermediate filaments, thus compromising mechanical strength and cell integrity. We report here the first mutation in a keratin gene (KRT1) that affects the variable tail domain (V2) and results in a profoundly different abnormality of the cytoskeletal architecture leading to a severe form of epidermal hyperkeratosis known as ichthyosis hystrix Curth-Macklin. Structural analyses disclosed a failure in keratin intermediate filament bundling, retraction of the cytoskeleton from the nucleus, and failed translocation of loricrin to the desmosomal plaques. These data provide the first in vivo evidence for the crucial role of a keratin tail domain in supramolecular keratin intermediate filament organization and barrier formation.

Amino Acid Sequence↗

PubMed2001

Human diploid fibroblasts that undergo a senescent-like differentiation have elevated ceramide and diacylglycerol.

Senescent human diploid fibroblasts (HDF) have elevated levels of ceramide and diacylglycerol (DAG) compared with young HDF. DNA fragmentation analysis demonstrated the increased ceramide in senescent HDF was not associated with apoptosis, whereas in young HDF, exogenous ceramide induced apoptosis. In young HDF treated with both exogenous ceramide and DAG, less DNA fragmentation was observed. Thus, elevated DAG levels in senescent HDF might protect against ceramide-induced apoptosis. To determine which characteristics of senescent HDF (aging per se, cell cycle arrest, elevated p21Sdi1,Waf1,Cip1, and senescent-like differentiation) might influence ceramide and DAG, we examined transformed or mitomycin C-treated HDF that shared some of these properties with senescent HDF. The elevation of ceramide and DAG did not depend on aging per se, cell cycle arrest, or elevation of p21. Rather, ceramide and DAG may be elevated as part of a program of differentiation that is induced by either aging or DNA damage.

Apoptosis↗

PubMed2001

Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors.

Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to <10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.

Animals↗

PubMed2001

Route of simian immunodeficiency virus inoculation determines the complexity but not the identity of viral variant populations that infect rhesus macaques.

A better understanding of the host and viral factors associated with human immunodeficiency virus (HIV) transmission is essential to developing effective strategies to curb the global HIV epidemic. Here we used the rhesus macaque-simian immunodeficiency virus (SIV) animal model of HIV infection to study the range of viral genotypes that are transmitted by different routes of inoculation and by different types of viral inocula. Analysis of transmitted variants was undertaken in outbred rhesus macaques inoculated intravenously (IV) or intravaginally (IVAG) with a genetically heterogeneous SIVmac251 stock derived from a well-characterized rhesus macaque viral isolate. In addition, we performed serial IV and IVAG passage experiments using plasma from SIV-infected macaques as the inoculum. We analyzed the V1-V2 region of the SIV envelope gene from virion-associated RNA in plasma from infected animals by the heteroduplex mobility assay (HMA) and by DNA sequence analysis. We found that a more diverse population of SIV genetic variants was present in the earliest virus-positive plasma samples from all five IV SIVmac251-inoculated monkeys and from two of five IVAG SIVmac251-inoculated monkeys. In contrast, we found a relatively homogeneous population of SIV envelope variants in three of five monkeys inoculated IVAG with SIVmac251 stock and in two monkeys infected after IVAG inoculation with plasma from an SIV-infected animal. In some IVAG-inoculated animals, the transmitted SIV variant was the most common variant in the inoculum. However, a specific viral variant in the SIVmac251 stock was not consistently transmitted by IVAG inoculation. Thus, it is likely that host factors or stochastic processes determine the specific viral variants that infect an animal after IVAG SIV exposure. In addition, our results clearly demonstrate that the route of inoculation is associated with the extent and breadth of the genetic complexity of the viral variant population in the earliest stages of systemic infection.

Administration, Intravaginal↗

PubMed2001

Tracking prostate carcinoma micrometastasis to multiple organs using histochemical marker genes and novel cell systems.

Studies of human prostate carcinoma (PCA) have been hampered by only a few cell systems from already-metastatic human disease. We have developed a novel cell system by using tissue cultured CWR22R cells from a xenograft of a primary tumor from a human patient. These cells were transfected with the bacterial lacZ gene to maximize their detection during progression and metastasis in nude mice. LZ-CWR22R cells are extremely stable for lacZ expression over 25 passages and metastasize to lung, liver, and bone from the subcutis - major sites of metastasis of the human disease. A matrigel vehicle facilitated development of primary tumors and micrometastases in all organs. While some micrometastases developed into overt metastases, others remained as micrometastases for long periods of time, possibly providing a model of latency of metastatic disease. An experimental metastasis model (tail vein injection) also generated micrometastases in lung, liver, and bone with differing kinetics of formation and stability. Serial sections of many individual lung micrometastases within one hour of injection indicated considerable heterogeneity in cellular composition (from 1 to 19 cells/site) while liver sites at later times were comprised of only 1 or 2 cells (the size of bone sites were comparable to those of liver). By combining use of these histochemically-tagged PCA cell systems with high resolution molecular analyses (laser-capture microdissection), it will now be possible to analyze gene expression patterns characteristic of micrometastases developing in several different organs.

Androgens↗

PubMed2000

Direct voltammetric investigation of the electrochemical properties of human hemoglobin: relevance to physiological redox chemistry.

Voltammetric measurements on solutions of human hemoglobin using gold electrodes modified with omega-hydroxyalkanethiols have yielded the first direct measure of the reorganization energy of the protein. The value obtained based on extrapolation of the experimentally measured currents, 0.76 eV, is independent of pH (i.e., over the physiologically relevant rage, pH 6.8-7.4) and is remarkably similar to values obtained for myoglobin. This result is perhaps surprising given the marked dependence of the measured reduction potential of hemoglobin on pH (i.e., the redox Bohr effect). Electron transfer rates from the electrode to hemoglobin were also measured. Using similarly measured heterogeneous electron-transfer rates for cytochrome b(5), it is possible to predict the magnitude of the homogeneous electron-transfer rate from cytochrome b(5) to methemoglobin using a formalism developed by Marcus. These predicted rates are in reasonable agreement with reported rates of this physiological reaction based on stopped-flow kinetics experiments. These results suggest that the intrinsic electroreactivity of these heme proteins is sufficient to account for physiologically observed rates. Residual differences between homogeneous phase kinetics and those predicted by heterogeneous phase reactions are suggested to be due to small reductions in the outer-sphere reorganization energy of both component proteins which arise due to solvent exclusion at the interface between the two proteins in complex.

Cytochromes b5↗

PubMed2000

Voltammetric probes of cytochrome electroreactivity: the effect of the protein matrix on outer-sphere reorganization energy and electronic coupling probed through comparisons with the behavior of porphyrin complexes.

Using surface-modified electrodes composed of omega-hydroxyalkanethiols, an experimentally based value for the inner-sphere reorganization energy of the bis(imidazole)iron porphyrin system has been obtained by examining the solvent dependence of the reorganization energy of bis(N-methylimidazole)meso-tetraphenyl iron porphyrin. The value obtained (0.41 +/- 0.06 eV) is remarkably similar to values we have recently reported for the reorganization energy of cytochrome b(5) (0.43 +/- 0.02 eV) and cytochrome c (0.58 +/- 0.06 eV). This strongly suggests that the protein matrix mimics the behavior of a low dielectric solvent and effectively shields the heme from the solvent. The effect of the orientation of the heme relative to the electrode was also explored by sytematically varying the steric bulk of the axial ligands. On the basis of a good linear correlation between the electronic coupling and the cosine of the angle between the heme plane and the surface of the electrode, it is suggested that a parallel orientation of the heme yields a maximum in the electronic coupling. Relevance to interheme protein electron transfer is discussed.

Animals↗

PubMed2000

Replication of simian immunodeficiency virus (SIV) in ex vivo lymph nodes as a means to assess susceptibility of macaques in vivo.

Six macaques, apparently uninfected, following low-dose exposure to the pathogenic SIV(mac251) and SIV(SME660) by the mucosal route, were used in a pilot study to investigate whether infectability of ex vivo lymph nodes could predict resistance and/or susceptibility to SIV infection in vivo. Of six macaques exposed to the less-pathogenic virus SIV(MNE), four resisted viral infection. Analysis of the susceptibility of the PBMC of these four animals before SIV(MNE) challenge indicated that all of them were resistant to infection by the SIV(BK28) isolate and, in three of them, this resistance was dependent on CD8+ T cells. Blocks of lymph nodes of these four macaques were resistant to SIV(MNE) infection ex vivo following SIV(MNE) viral challenge exposure. However, the same blocks from the same animals were permissive to the more virulent SIV(251(32H)). Accordingly, three of these macaques were readily infected following challenge exposure with SIV(251(32H)). Lymphoproliferative responses in blood or lymph nodes, local C-C chemokine production in the lymph-node explants, and cytotoxic T-cell activity measured throughout the study did not correlate with ex vivo resistance or susceptibility to in vivo infection. In conclusion, PBMC and lymph-node resistance or susceptibility to infection ex vivo appeared to correlate with in vivo infectivity and, thus, these approaches should be further tested for their predictive value for in vivo infection.

Animals↗

PubMed2000

Antigen-dependent cytokine mRNA expression by individual rhesus macaque T helper cells by flow cytometry.

Specific patterns of cytokine secretion by CD4(+) T helper (Th) cells determine the nature of immune effector responses. Using a multiparameter, flow cytometric fluorescent in situ hybridization (FISH) assay that detected cytoplasmic mRNA within intact cells, we assessed antigen-specific cytokine expression in rhesus macaque Th cells. In the peripheral lymphocytes of immunized rhesus macaques, FISH detected antigen-induced cytokine gene expression in single Th cells. Analysis of simultaneous cytokine expression by single cells demonstrated that the recall immune response consisted of Th cells expressing either a Th1 (IL-2(+)/IFN-gamma(+)) or a Th2 (IL-4(+)/IL-6(+)) cytokine pattern. In addition to the classic Th subsets, Th cells expressing only one of two Th1 or Th2 defining cytokines were common following antigen restimulation. The data gathered with the FISH assay suggest that, in primates, the immune response to recall antigens consists of nonclassic Th cells, as well as a mixture of polarized Th1 and Th2 T cells.

Animals↗

PubMed2000

Effectiveness and tolerability of zafirlukast for the treatment of asthma in children.

OBJECTIVE: This study was undertaken to examine the dose-response relationship of zafirlukast (5 to 40 mg BID) and to assess the efficacy and tolerability of the 10-mg BID dose in school-aged children with mild to moderate asthma. BACKGROUND: The efficacy and tolerability of zafirlukast, an oral leukotriene-receptor antagonist, has been demonstrated in adolescents and adults aged > or = 12 years. METHODS: Data from 2 placebo-controlled, parallel-group, multicenter trials (trial 1, 4-week double-blind; trial 2, 6-week double-blind) were integrated. Children aged 5 to 11 years were randomly assigned to receive zafirlukast 5 mg BID (n = 99), 10 mg BID (n = 205), 20 mg BID (n = 105), 40 mg BID (n = 99), or placebo (n = 206). The primary outcome was change from baseline in forced expiratory volume in 1 second (FEV1) expressed as percent of predicted normal. Secondary outcomes were FEV1 (L), morning and evening peak expiratory flow, peak flow variability, short-acting beta2-agonist use, asthma episode score, and nights awakened by asthma. RESULTS: Mean baseline FEV1 was 76.5% of predicted. The greatest improvements were generally seen with zafirlukast 5 mg BID or 10 mg BID, with no additional clinically significant benefits seen at higher doses. The pooled data analysis showed that 10 mg BID compared with placebo significantly improved (P < 0.045) all efficacy outcomes except asthma-episode score and nights awakened with asthma. However, in the subset of children who had > or = 1 night awakened per week at baseline (zafirlukast 10 mg BID = 78; placebo = 86), 10 mg BID significantly reduced nights awakened (P = 0.009) (mean difference from placebo at end point = -0.81 night/wk). All zafirlukast doses were well tolerated and had tolerability profiles that were clinically indistinguishable from placebo. CONCLUSION: These results support the effectiveness and tolerability of the 10-mg BID dose of zafirlukast for the prophylaxis and chronic treatment of mild to moderate asthma in children.

Adolescent↗

PubMed2000

Isolation and characterization of fungal inhibitors from Epichloë festucae.

A series of studies was conducted to test the antifungal activity of clavicipitaceous endophytes and to identify potential fungal inhibitors in this symbiotic infection. A diverse group of endophytes was screened for antifungal activity using organic extracts from liquid fermentation cultures. Fungal inhibitors were purified from fermentation cultures of Epichloë festucae using a bioassay-directed extraction with Cryphonectria parasitica as the test organism. Compounds shown to have antifungal activity were subsequently identified using NMR and GC-MS. Extracts from a wide range of fungal isolates had various degrees of antifungal activity, but the greatest antifungal activity was observed in E. festucae and Neotyphodium tembladerae. Three types of inhibitors were isolated from a batch culture of E. festucae, including several indole derivatives, a sesquiterpene, and a diacetamide. Among the indole derivatives, indole-3-acetic acid and indole-3-ethanol were identified as the major indoles. These compounds were previously reported in endophytic fungi, and this study suggests a role in host disease resistance against other pathogens. The diversity in fungal inhibitors produced by this endophyte also suggests that fungal inhibitors may act additively or synergistically to reduce colonization of endophyte-infected hosts by potential fungal competitors.

Antifungal Agents↗

PubMed2000

Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells.

Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR(+)-enriched cell suspensions to identify the cells containing SIV RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA(+) DC were documented in cell suspensions from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa. We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV-infected cells are located in draining lymph nodes within 18 h of intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining lymph nodes poses a serious challenge to HIV vaccine development.

Administration, Intravaginal↗

PubMed2000

Simian-human immunodeficiency virus containing a human immunodeficiency virus type 1 subtype-E envelope gene: persistent infection, CD4(+) T-cell depletion, and mucosal membrane transmission in macaques.

The envelope (env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) determines several viral properties (e.g., coreceptor usage, cell tropism, and cytopathicity) and is a major target of antiviral immune responses. Most investigations on env have been conducted on subtype-B viral strains, prevalent in North America and Europe. Our study aimed to analyze env genes of subtype-E viral strains, prevalent in Asia and Africa, with a nonhuman primate model for lentivirus infection and AIDS. To this end, we constructed a simian immunodeficiency virus/HIV-1 subtype-E (SHIV) recombinant clone by replacing the env ectodomain of the SHIV-33 clone with the env ectodomain from the subtype-E strain HIV-1(CAR402), which was isolated from an individual in the Central African Republic. Virus from this recombinant clone, designated SHIV-E-CAR, replicated efficiently in macaque peripheral blood mononuclear cells. Accordingly, juvenile macaques were inoculated with cell-free SHIV-E-CAR by the intravenous or intravaginal route; virus replicated in these animals but did not produce hematological abnormalities. In an attempt to elicit the pathogenic potential of the recombinant clone, we serially passaged this viral clone via transfusion of blood and bone marrow through juvenile macaques to produce SHIV-E-P4 (fourth-passage virus). The serially passaged virus established productive infection and CD4(+) T-cell depletion in juvenile macaques inoculated by either the intravenous or the intravaginal route. Determination of the coreceptor usage of SHIV-E-CAR and serially passaged SHIV-E-P4 indicated that both of these viruses utilized CXCR4 as a coreceptor. In summary, the serially passaged SHIV subtype-E chimeric virus will be important for studies aimed at developing a nonhuman primate model for analyzing the functions of subtype-E env genes in viral transmission and pathogenesis and for vaccine challenge experiments with macaques immunized with HIV-1 env antigens.

Acquired Immunodeficiency Syndrome↗