Publications
127 results found
Harman SJ, Herrera C, Armanasco N, et al., 2010, L'644, a cholesterol derivatized version of the gp41 fusion peptide C34, provides superior activity in preclinical microbicide assays (oral presentation given by C Herrera), 17th Conference on Retroviruses and Opportunistic Infections
Herrera C, Cranage M, McGowan I, et al., 2010, Using drug combinations to design colorectal microbicides:where is the limit?, HIV Biology and Pathogenesis (A6)
Receptive anal intercourse is associated with the highest probability for sexual HIV infection. Drug combinations need to be considered in the design of an effective microbicide against wild type and resistant HIV-1 isolates. The antiviral efficacy of two nucleosides reverse transcriptase inhibitors (NRTI) PMPA and FTC, and two non-NRTIs (NNRTI) UC-781 and TMC120, used in double, triple and quadruple combinations, was assessed against clade B HIV-1 isolates. All combinations inhibited the isolates tested in TZM-bl cells and colorectal explants, and produced, for at least one of the compounds, a change in the dose response curve. Double and triple combinations incrementally augmented activity, even against RTI escape mutants, whereas quadruple combinations conferred little further advantage. The colorectal explant model is key to identification of the best candidate molecules and their combinations at the preclinical stage. Furthermore, this study demonstrates that combinations based on compounds with different HIV-1 inhibitory mechanisms have potential as colorectal microbicides.
Herrera C, Cranage M, McGowan I, et al., 2009, Designing colorectal microbicides with reverse transcriptase inhibitor combinations.(Oral communication by C. Herrera), Annual Europrise Meeting 2009
Abraha A, Nankya IL, Gibson R, et al., 2009, CCR5-and CXCR4-Tropic Subtype C Human Immunodeficiency Virus Type 1 Isolates Have a Lower Level of Pathogenic Fitness than Other Dominant Group M Subtypes: Implications for the Epidemic, JOURNAL OF VIROLOGY, Vol: 83, Pages: 5592-5605, ISSN: 0022-538X
- Author Web Link
- Cite
- Citations: 78
Herrera C, Cranage M, McGowan I, et al., 2009, Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 53, Pages: 1797-1807, ISSN: 0066-4804
- Author Web Link
- Cite
- Citations: 75
Herrera C, McRaven M, Hope T, et al., 2009, Early colorectal responses to HIV-1 and modulation by microbicides. (Oral communication by C. Herrera), Prevention of HIV/AIDS (X3)
The extreme vulnerability of the colorectal tract to HIV-1 infection is likely due to histological and immunological characteristics of the intestinal mucosae. Viral exposure studies using fluorescent BaLPAGFPGag demonstrated virus penetration of up to 39 m into the lamina propia within 6 h. Early responses to viral exposure were analyzed by Luminex and RNA microarray, at two set time points: 6 h (representing responses induced by viral attachment, entry and early reverse transcription) and 24 h (corresponding to viral integration and productive infection). HIV exposure to tissue for 6 h induced an increase in the levels of IL-1, IL-1, IL-6, IL-8, MCP-1 and GCSF secretion. Further secretion of these pro-inflammatory cytokines was detected after 24 h of incubation independently of viral tropism. The X4-isolate NL4.3 induced higher levels of RANTES, MIP-1 and MIP-1secretion than R5-HIV-1 YU.2. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. This work was funded by amfAR grant 106756-41-RFMT.
Herrera C, Cranage M, McGowan I, et al., 2009, Reverse transcriptase inhibitors as potential colorectal microbicides, Antimicrob Agents Chemother, Vol: 53, Pages: 1797-1807
We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI- and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.
Abraha A, Nankya IL, Gibson R, et al., 2009, CCR5- and CXCR4-tropic subtype C human immunodeficiency virus type 1 isolates have a lower level of pathogenic fitness than other dominant group M subtypes: implications for the epidemic, J Virol, Vol: 83, Pages: 5592-5605
Human immunodeficiency virus type 1 (HIV-1) subtype C is the dominant subtype globally, due largely to the incidence of subtype C infections in sub-Saharan Africa and east Asia. We compared the relative replicative fitness (ex vivo) of the major (M) group of HIV-1 subtypes A, B, C, D, and CRF01_AE and group O isolates. To estimate pathogenic fitness, pairwise competitions were performed between CCR5-tropic (R5) or CXCR4-tropic (X4) virus isolates in peripheral blood mononuclear cells (PBMC). A general fitness order was observed among 33 HIV-1 isolates; subtype B and D HIV-1 isolates were slightly more fit than the subtype A and dramatically more fit than the 12 subtype C isolates. All group M isolates were more fit (ex vivo) than the group O isolates. To estimate ex vivo transmission fitness, a subset of primary HIV-1 isolates were examined in primary human explants from penile, cervical, and rectal tissues. Only R5 isolates and no X4 HIV-1 isolates could replicate in these tissues, whereas the spread to PM1 cells was dependent on active replication and passive virus transfer. In tissue competition experiments, subtype C isolates could compete with and, in some cases, even win over subtype A and D isolates. However, when the migratory cells from infected tissues were mixed with a susceptible cell line, the subtype C isolates were outcompeted by other subtypes, as observed in experiments with PBMC. These findings suggest that subtype C HIV-1 isolates might have equal transmission fitness but reduced pathogenic fitness relative to other group M HIV-1 isolates.
Cranage M, Sharpe S, Dennis M, et al., 2008, Stimulating immunity to HIV at the virus portal of entry. (Oral communication), Modern Mucosal Vaccines and Microbicides 2008
Cranage M, Sharpe S, Herrera C, et al., 2008, Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel, PLoS Medicine, Vol: 5, ISSN: 1549-1277
BACKGROUND: The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. METHODS AND FINDINGS: A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from
Cranage M, Sharpe S, Herrera C, et al., 2008, Rectal prophylaxis with tenofovir protects macaques and facilitates the priming of SIV-specific T cells. (Oral communcation), ICMS Symposium: HIV research in 2008
Herrera C, Cranage M, McGowan I, et al., 2008, Reverse transcriptase inhibitors as potential colorectal microbicides., HIV Pathogenesis (X8)
Herrera C, Cranage M, McGowan I, et al., 2008, Reverse transcriptase inhibitors as potential colorectal microbicides. (Oral Communication by C. Herrera), Microbicides 2008
Cranage M, Sharpe S, Herrera C, et al., 2007, Pre-exposure [prophylaxis in macaques against rectal SIV challenge by mucosally-applied PMPA: potential for complementation of microbicide and vaccination strategies. (Oral communication), Annual Europrise Meeting 2007
Cranage M, Sharpe S, Cope A, et al., 2007, Pre-exposure prophylaxis in macaques against rectal SIV challenge by mucosally applied PMPA: potential for complementation of microbicide and vaccination strategies. (Oral Communication), CROI 2007
Herrera C, Kake S, Kibler C, et al., 2007, Consequences of HIV-1 Env cleavage on antigenicity , infectivity and neutralization. (Oral communication by C. Herrera), Virtual Virology
Cranage M, Sharpe S, Cope A, et al., 2006, Systemic T cel priming in macaques exposed rectally to SIV after local application of a nucleotide analogue reverse trancriptase inhibitor, AIDS Vaccine 2006
Background: Rectal transmission is a significant route for the acquisition of HIV driving the requirement for the development of rectally applied prophylactic microbicides as a prevention strategy that may be complementary to vaccination.Objectives: (1) To determine, in the macaque model, the antiviral efficacy of the nucleotide analogue, 9-[(R)-2-(phosphonmethoxy) propyl] adenine monohydrate (PMPA) given rectally as a single dose prior to, or shortly after, intrarectal challenge with simian immunodeficiency virus (SIV). (2) To determine if mucosal exposure to virus primes immunity in animals protected from overt infection by locally applied PMPA. Methods: Rhesus macaques received 1% PMPA gel in a single dose by atraumatic rectal instillation. Twenty intrarectal median infectious dose (MID50) of SIVmac32H was used for challenge. Peripheral blood mononuclear cells (PBMC) were examined for the presence of virus by PCR for proviral DNA and by co-cultivation at regular intervals over 20 weeks. Results: Virus was recovered at every time point tested in 4 of 4 untreated macaques and 3 of 4 animals given placebo gel. In contrast, 6 of 9 animals given PMPA prior to virus challenge were protected from virus challenge and virus detection was intermittent or delayed in 2 other animals. Virus was isolated on every occasion of testing from 2 of 3 animals where gel was administered 2 hours after virus challenge. Corresponding results were obtained by PCR analysis. Apparently protected animals had no evidence of viral sequestration in lymphoid tissues and failed to seroconvert. Protection was associated with the concentration of PMPA detected in plasma at the time of virus challenge. Interestingly, Gag-specific interferon-gamma secreting T cells were detected by ELISpot in 4 of 7 animals in which virus was unrecoverable from PBMC at frequencies ranging from 144 spot forming cells (SFC)/106 PBMC to 261 SFC/106 PBMC.Conclusions: These data indicate that rectal predosing with PMPA ha
Cranage M, Sharpe S, Cope A, et al., 2006, Protection of macaques against rectal SIV challenge by mucosally-applied PMPA. (Oral Communication), Microbicides 2006
Herrera C, Klasse PJ, Kibler CW, et al., 2006, Dominant-negative effect of hetero-oligomerization on the function of the human immunodeficiency virus type 1 envelope glycoprotein complex, Virology, Vol: 351, Pages: 121-132
The human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein forms trimers that mediate interactions with the CD4 receptor and a co-receptor on the target cell surface, thereby triggering viral fusion with the cell membrane. Cleavage of Env into its surface, gp120, and transmembrane, gp41, moieties is necessary for activation of its fusogenicity. Here, we produced pseudoviruses with phenotypically mixed wild-type (Wt) and mutant, cleavage-incompetent Env in order to quantify the effects of incorporating uncleaved Env on virion infectivity, antigenicity and neutralization sensitivity. We modeled the relative infectivity of three such phenotypically mixed viral strains, JR-FL, HXBc2 and a derivative of the latter, 3.2P, as a function of the relative amount of Wt Env. The data were fit very closely (R(2) > 0.99) by models which assumed that only Wt homotrimers were functional, with different approximate thresholds of critical numbers of functional trimers per virion for the three strains. We also produced 3.2P pseudoviruses containing both a cleavage-competent Env that is defective for binding the neutralizing monoclonal antibody (NAb) 2G12, and a cleavage-incompetent Env that binds 2G12. The 2G12 NAb was not able to reduce the infectivity of these pseudoviruses detectably. Their neutralization by the CD4-binding site-directed agents CD4-IgG2 and NAb b12 was also unaffected by 2G12 binding to uncleaved Env. These results further strengthen the conclusion that only homotrimers consisting of cleaved Env are functional. They also imply that the function of a trimer is unaffected sterically by the binding of an antibody to an adjacent trimer.
Marozsan AJ, Kuhmann SE, Morgan T, et al., 2005, Generation and properties of a human immunodeficiency virus type 1 isolate resistant to the small molecule CCR5 inhibitor, SCH-417690 (SCH-D), Virology, Vol: 338, Pages: 182-199
We describe the generation of two genetically related human immunodeficiency virus type 1 (HIV-1) isolates highly (>20,000-fold) resistant to the small molecule CCR5 inhibitor, SCH-417690 (formerly SCH-D). Both viruses were cross-resistant to other small molecules targeting entry via CCR5, but they were inhibited by some MAbs against the same coreceptor on primary CD4+ T-cells. The resistant isolates remained sensitive to inhibitors of other stages of virus entry, and to replication inhibitors acting post-entry. Neither escape mutant could replicate detectably in peripheral blood mononuclear cells (PBMC) from two donors homozygous for the CCR5-Delta32 allele and both were insensitive to the CXCR4-specific inhibitor, AMD3100. Hence, the SCH-D escape mutants retained the R5 phenotype. One of the resistant isolates was, however, capable of replication in U87.CD4.CXCR4 cells and, after expansion in those cells, was sensitive to AMD3100 in primary CD4+ T-cells. Hence, some X4 variants may be present in this escape mutant swarm. A notable observation was that the SCH-D escape mutants were also cross-resistant to PSC-RANTES and AOP-RANTES, chemokine derivatives that are reported to down-regulate cell surface CCR5 almost completely. However, the extent to which CCR5 is down-regulated was dependent upon the detection MAb. Hence, the escape mutants may be using a CCR5 configuration that is only detected by some anti-CCR5 MAbs. Finally, two SCH-D-resistant clonal viruses revealed no amino acid changes in the gp120 V3 region relative to the parental viruses, in marked contrast to clones resistant to the AD101 small molecule CCR5 inhibitor that possess 4 such sequence changes. Several sequence changes elsewhere in gp120 (V2, C3 and V4) were present in the SCH-D-resistant clones. Their influence on the resistant phenotype remains to be determined.
Beddows S, Zheng NN, Herrera C, et al., 2005, Neutralization sensitivity of HIV-1 Env-pseudotyped virus clones is determined by co-operativity between mutations which modulate the CD4-binding site and those that affect gp120-gp41 stability, Virology, Vol: 337, Pages: 136-148
Adaptation of antibody neutralization-resistant human immunodeficiency virus type I (HIV-1) to growth in vitro generally results in the acquisition of a neutralization-sensitive phenotype, an alteration of viral growth kinetics, and an array of amino acid substitutions associated with these changes. Here we examine a panel of Env chimeras and mutants derived from these neutralization-resistant and -sensitive parental Envs. A range of neutralization and infectivity phenotypes was observed. These included a modulation of the CD4 binding site (CD4bs) towards recognition by neutralizing and non-neutralizing CD4bs-directed antibodies, resulting in a globally neutralization-sensitive Env; alterations which affected Env complex stability; and interactions which resulted in differential infectivity and CCR5/CXCR4 usage. This range of properties resulted from the complex interactions of no more than three amino acids found in key Env locations. These data add to a growing body of evidence that dramatic functional alterations of the native oligomeric Env protein complex can result from relatively minor amino acid substitutions.
Herrera C, Klasse PJ, Michael E, et al., 2005, The impact of envelope glycoprotein cleavage on the antigenicity, infectivity, and neutralization sensitivity of Env-pseudotyped human immunodeficiency virus type 1 particles, Virology, Vol: 338, Pages: 154-172
Endoproteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoproteins is an obligate part of the biosynthetic pathway that generates functional, fusion-competent Env complexes, which are then incorporated into infectious virions. We have examined the influence of cleavage on Env-specific antibody reactivity, Env incorporation into pseudovirions, and the infectivity and neutralization sensitivity of Env-pseudotyped viruses. To do so, we have used both incompletely processed wild-type (Wt) Env and engineered, cleavage-defective Env mutants. We find that there is no simple association between antibody reactivity to cell surface-expressed Env, and the ability of the same antibody to neutralize virus pseudotyped with the same Env proteins. One explanation for the absence of such an association is the diverse array of Env species present on the surface of transiently transfected cells. We also confirm that cleavage-defective mutants are antigenically different from Wt Env. These findings have implications for the use of Env binding assays as predictors of neutralizing activity, and for the development of cleavage-defective Env trimers for use as subunit immunogens.
Herrera C, Michael E, Kake S, et al., 2004, Consequences of HIV-1 Env cleavage on antigenicity, infectivity and neutralization.(Poster and Oral Communication by C. Herrera), HIV Vaccine Development: Progress and Prospects (X8)
Herrera C, Kake S, Michael E, et al., 2003, Consequences of HIV-1 Env cleavage on antigenicity, infectivity and neutralization. (Oral communication), AIDS Vaccine 2003
Dumaurier MJ, Kuhmann S, Herrera C, et al., 2003, Study of HIV-1 entry inhibitors at a cellular level., HIV Vaccine Development: Immunological and Biological Challenges (X1)
Herrera C, Spenlehauer C, Fung MS, et al., 2003, Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site., HIV Vaccine Development: Immunological and Biological Challenges (X1)
Herrera C, Spenlehauer C, Fung MS, et al., 2003, Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site, J Virol, Vol: 77, Pages: 1084-1091
We have investigated whether nonneutralizing monoclonal antibodies (MAbs) to the gp120 subunit of the envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 (HIV-1) can interfere with HIV-1 neutralization by another anti-gp120 MAb. We used neutralizing (b12) and nonneutralizing (205-42-15, 204-43-1, 205-46-9) MAbs to the epitope cluster overlapping the CD4-binding site (CD4BS) on gp120. All the MAbs, neutralizing or otherwise, cross-competed for binding to monomeric gp120, indicating the close topological proximity of their epitopes. However, the nonneutralizing CD4BS MAbs did not interfere with the neutralization activity of MAb b12. In contrast, in a binding assay using oligomeric Env expressed on the surface of Env-transfected cells, the nonneutralizing MAbs did partially compete with b12 for Env binding. The surface of Env-transfected cells contains two categories of binding site for CD4BS MAbs. One type of site is recognized by both b12 and nonneutralizing CD4BS MAbs; the other is recognized by only b12. Binding assays for Env-gp120 interactions based on the use of monomeric gp120 or Env-transfected cells do not predict the outcome of HIV-1 neutralization assays, and they should therefore be used only with caution when gauging the properties of anti-Env MAbs.
Herrera C, Casado V, Ciruela F, et al., 2001, Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells, Mol Pharmacol, Vol: 59, Pages: 127-134
Adenosine deaminase (ADA) is an enzyme of the purine metabolism that has been largely considered to be cytosolic. Recently, it has been demonstrated that the enzyme appears on the surface of lymphocytes where it interacts with the T-cell activation antigen CD26. ADA also appears on the surface of nonlymphoid cells anchored to adenosine A1 receptors. Here it is demonstrated that cell surface ADA in ADA+/CD26- T lymphocytes anchors to adenosine receptors of the A2B subtype (A2BR). An interaction between A2BR and cell surface ADA has been demonstrated in transfected Chinese hamster ovary cells and Jurkat J32 T lymphocytes. This has been proved by coimmunoprecipitation, binding of exogenous ADA to A2BR+ cells, and coimmunolocalization. The specificity of the interaction has also been demonstrated by the lack of interaction with other members of the G protein-coupled receptor superfamily. Binding of ADA to A2BR increases the affinity of the agonist 5'-N-ethylcarboxamidoadenosine and cAMP production. This effect occurs even when ADA devoid of enzyme activity is used. Therefore, in lymphocytes, cell surface ADA, apart from degrading extracellular adenosine, regulates those actions of adenosine that are mediated via adenosine receptors of the A2B subtype.
Cordero OJ, Salgado FJ, Fernandez-Alonso CM, et al., 2001, Cytokines regulate membrane adenosine deaminase on human activated lymphocytes, J Leukoc Biol, Vol: 70, Pages: 920-930
CD26 is a lymphocyte marker that can anchor adenosine deaminase (ADA) on the T cell surface. We found that ADA is regulated by cytokines on the cell surface during T cell activation. By means of flow cytometry, immunofluorescence, and immunoblotting techniques, we found that interleukin (IL)-2 and IL-12 up-regulate ecto-ADA and CD26 expression. In clear contrast, IL-4 led to down-regulation of lymphocyte surface ADA without modifying the level of CD26. Moreover, neither circulating ADA transcription nor mRNA translation was regulated by cytokines. These results, along with absence of total-ADA modulation, the variable amount of ADA found in purified plasma membranes, and the different effect of Brefeldin A on the surface presence of ADA and CD26 indicated that cytokines regulate the translocation of ADA towards the cell surface through a mechanism not involving CD26. Ecto-ADA protected activated lymphocytes from the toxic effects of extracellular adenosine. Therefore, this cell surface ADA control might constitute part of the fine immunoregulatory mechanism of adenosine-mediated signaling through purinergic receptors in leukocytes.
Herrera C, Morimoto C, Blanco J, et al., 2001, Comodulation of CXCR4 and CD26 in human lymphocytes, J Biol Chem, Vol: 276, Pages: 19532-19539
We provide convergent and multiple evidence for a CD26/CXCR4 interaction. Thus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membranes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal cell-derived factor 1alpha (SDF-1alpha), CD26 is cointernalized with CXCR4. CXCR4-mediated down-regulation of CD26 is not induced by antagonists or human immunodeficiency virus (HIV)-1 gp120. SDF-1alpha-mediated down-regulation of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1alpha, the CXCR4.CD26 complex is likely a functional unit in which CD26 may directly modulate SDF-1alpha-induced chemotaxis and antiviral capacity. CD26 anchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this interaction is blocked by HIV-1 gp120. Here we demonstrate that gp120 interacts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecular structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.