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PubMed1994

Alpha 6 integrin distribution in human embryonic and adult tissues.

Alpha 6 integrin is an adhesion molecule that connects cells with extracellular matrix molecules of the laminin family. The laminin interaction seems to be essential for cell differentiation during embryogenesis and for the subsequent maintenance of tissue integrity in the adult. Alpha 6 integrin can also interact with laminin-independent cellular ligands and in this way plays a role in homing of leucocytes. Furthermore, in cancer biology alpha 6 integrin has an important role in metastasis and as a possible new prognostic factor; exact knowledge of alpha 6 integrin distribution in normal human tissues is therefore a crucial element. By immuno-histochemical methods we have screened alpha 6 integrin expression of representative human tissues from the adult and the embryonic organism. All tested epithelia were alpha 6 integrin positive, except for the endocrine cells of the pancreas and the adrenal glands. Heterogeneous staining was found on non-epithelial tissues. Strong staining was evident in peripheral nerves (Schwann cells), germ and Sertoli cells, endothelia, and smooth muscle cells of the myometrium. Weak staining was found in nerve cells of the stratum granulosum, the microglia, Kupffer's cells and stromal cells of the ovary. All fibroblasts, striated muscle cells and astrocytes were negative. The tissue distribution of alpha 6 integrin and the semi-quantitative estimation of their expression level should provide a better understanding of alpha 6 integrin function under normal and pathological conditions, in particular in tumour progression.

Adult↗

PubMed1995

Growth factor regulation of integrin-mediated cell motility.

Cell motility, a primary component of tumor cell invasion, is a continuum of sequential events in which the cell extends pseudopodia, forms nascent attachments, assembles and contracts the cytoskeleton, and finally, as it translocates forward, disengages distal adhesions. What triggers cells to move? Substratum contact mediated by integrin adhesion receptors is important, but other signals such as chemokinetic factors appear to be required for continued crawling. It is now apparent that integrins do not simply bind cells to matrix in a Velcro-like fashion, but also are potent signaling molecules. Initial engagement of integrins induces their condensation into focal contacts, forming anchors to the extracellular matrix and discrete signal-transducing complexes on the cytoplasmic surface. A number of growth factors, through either autocrine or paracrine pathways, can activate the cellular machinery that mobilizes the cell. Thus, these two classes of receptors--the integrin receptors that bind specific extracellular adhesion molecules, and growth factor receptors that bind their respective ligands--can regulate cell locomotion. Not surprisingly, there is 'cross-talk' between integrin and growth factor receptors that occurs through their common intracellular signaling pathways. In this way, each receptor type can either amplify or attenuate the other's signal and downstream response. An example of growth factor-induced motility is the epithelial-mesenchymal transition induced by hepatocyte growth factor/scatter factor (HGF/SF). When bound to its receptor, the c-met proto-oncogene product, HGF/SF induces a phenotypic conversion that appears to be an important aspect of tumor progression in malignant carcinomas. The motogenic response produced by HGF/SF in carcinoma cells occurs in discrete steps in which integrins and focal adhesion kinase (p125FAK) are first recruited to focal contacts. This is rapidly followed by cell spreading, disruption of focal adhesions and cell-cell contacts, and, finally, cell crawling. The precise mechanism by which growth factors such as HGF/SF and its receptor induce this motogenic response and modulate integrin function has not been clearly defined but appears to involve several signaling pathways. Understanding the process by which growth factor and integrin receptors interact and regulate motility may suggest novel targets for therapeutic intervention.

Animals↗

PubMedDate not supplied

Expression and role of integrins in adhesion of human colonic carcinoma cells to extracellular matrix components.

We have examined integrin expression and function in the human colon carcinoma cell line HT29, and in clonal sublines derived from the HT29 line. These cells express several different integrin subunits including beta 1, alpha 2, 3, 6 and alpha v, but do not express the classic alpha 5/beta 1 fibronectin receptor. Clonal variation in the pattern of integrin expression was quite limited. The profile of integrin expression correlates well with the adhesive behavior of HT29 cells. Thus the cells adhere well to vitronectin, laminin and type IV collagen, but not at all to fibronectin. Adhesion to collagen was completely blocked by an anti-beta 1 monoclonal antibody, indicating that beta 1 integrins mediate this process. Adhesion to laminin was strongly blocked by anti-beta 1 monoclonal or anti-beta 6 monoclonal, suggesting that the alpha 6/beta 1 complex functions in attachment to laminin; this was somewhat surprising since immunoprecipitation experiments indicate that most of the alpha 6 subunit seems to be associated with the beta 4 subunit. Despite their strong adherence to laminin, collagen and vitronectin, HT29 cells are not very motile and, in response to gradients of these proteins, do not migrate nearly as well as CHO cells tested under similar conditions. Since HT29 cells can undergo an enterocyte-like differentiation in glucose-free medium, we compared integrin expression in HT29 and its subclones during the process of differentiation. There was no correlation between the state of differentiation, as assessed by expression of brush-border hydrolases, and the level of expression of any of the integrin subunits measured. Thus the pattern of integrin expression in these colonic tumor cells seems to be a characteristic of the cell line, and is not readily modified by changes in cell growth or differentiation.

Carcinoma↗

PubMed1996

Role of laminin and integrin interactions in growth cone guidance.

Laminin is well known to promote neuronal adhesion and axonal growth, but recent experiments suggest laminin has a wider role in guiding axons, both in development and regeneration. In vitro experiments demonstrate that laminin can alter the rate and direction of axonal growth, even when growth cone contact with laminin is transient. Investigations focused on a single neuronal type, such as retinal ganglion cells (RGCs), strongly implicate laminin as an important guidance molecule in development and suggest the involvement of integrins. Integrins are receptors for laminin, and neurons express multiple types of integrins that bind laminin. Morphologically, integrins cluster in point contacts, specialized regions of the growth cone that may coordinately regulate adhesion and motility. Recent evidence suggests that the structure and regulation of point contacts may differ from that of their nonneuronal counterpart, focal contacts. In part, this may be because the interaction of the cytoplasmic domain of integrin with the cytoskeleton is different in point contacts and focal contracts. Mutational studies where the cytoplasmic domain is truncated or altered are leading to a better understanding of the role of the alpha and beta subunit in regulating integrin clustering and binding to the cytoskeleton. In addition, whereas integrins may regulate motility through direct physical linkages to the growth cone cytoskeleton, an equally important role is their ability to elicit signaling, both through protein tyrosine phosphorylation and modulating calcium levels. Through such mechanisms integrins likely regulate the dynamic attachment and detachment of the growth cone as it moves on laminin substrates.

Animals↗

PubMed1993

Immunolocalization of integrins in the normal and neoplastic colonic epithelium.

Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin. In NC, alpha 2 staining was strongest in crypt cells; alpha 1,3 and alpha v, and beta 1,3 and beta 4, and Ck 20 and villin predominated in superficial enterocytes. In TA and VA, monolayered glands showed integrin, Ck 20 and villin patterns that differed slightly from both crypt and superficial enterocytes. Complex glands in VA showed decreased integrin staining and basal polarization; Ck 20 and villin were strong only in luminal cells. CA showed overall weaker integrin staining than adenomas. Regardless of invasion depth, well formed malignant glands mimicked TA; pleomorphic glands mimicked VA with focal basal integrin polarization and solid clusters displayed scanty integrins, uneven Ck 20, and villin in occasional cells. Diverse integrins in crypt compared with superficial enterocytes reflect changing adhesive requirements as cells migrate and terminally differentiate. Decreasing expression and altered distribution of integrins, Ck 20 and villin noted in TA, VA, and in CA of increasing grade indicate that certain adhesive and cytoskeletal features more closely relate to glandular architecture than to depth of invasion.

Adenocarcinoma↗

PubMed1996

The vitronectin receptor (alpha V beta 3) as an example for the role of integrins in T lymphocyte stimulation.

Integrins are a family of cell surface receptors which mediate the adhesion of cells to each other or to extracellular matrix (ECM) proteins. The interaction of integrins with their ligands or counter-receptors was initially considered to be a one-way process in that cells actively regulate the interaction of integrins with their ligands ('inside-out signal'). In contrast, it was not obvious that cells would receive a signal from the outside via the integrin heterodimers following ligand binding ('outside-in signal'). Recent evidence increasingly supports the active role of integrins in cell activation and proliferation. Many reports describe the effects of integrin-mediated signaling in lymphoid cells. Our studies of gamma/delta T cells, expressing the beta 3 integrin vitronectin receptor (VNR), reflect some of the consequences this active interaction between lymphocytes and the ECM could have for T cell activation and differentiation. The VNR has been described as a T cell costimulatory molecule. We recently reported that the VNR has the potential to stimulate cytokine secretion in T cell hybridomas without involvement of T cell receptor-mediated signals. Further studies demonstrated tyrosine phosphorylation of proteins following VNR cross-linking and the interaction of the VNR with protein kinases. Intensive research focuses on the signal transduction mechanisms of integrins and their interaction with other costimulatory or activation molecules. This knowledge is important to better understand the role of adhesion molecules, the ECM, and the cellular microenvironment for lymphocyte activation and differentiation.

Animals↗

PubMed1998

Integrin-mediated signal transduction.

Integrins, expressed on virtually every cell type, are proteins that mediated cellular interactions with components of the extracellular matrix (ECM) and cell surface integral plasma membrane proteins. In addition, integrins interact with the cytoskeleton and through this process participate in cell migration, tissue organization, cell growth, haemostasis, inflammation, target recognition of lymphocytes and the differentiation of many cell types. Signals generated from ligand-integrin interactions are propagated via the integrin cytoplasmic tails to signal transduction pathways within the cell (outside-in signalling). Information from within the cell can also be transmitted to the outside via integrin affinity modulation (inside-out signalling). Protein tyrosine phosphorylation has a central role in integrin-initiated cell signalling, leading to cytoskeletal organization and focal adhesion formation. This review will examine the current understanding of integrin function, focusing on the intracellular consequences of integrin-ligand interaction.

Calcium↗

PubMed2001

Evolution of the integrin alpha and beta protein families.

A phylogenetic analysis of vertebrate and invertebrate alpha integrins supported the hypothesis that two major families of vertebrate alpha integrins originated prior to the divergence of deuterostomes and protostomes. These two families include, respectively, the alpha PS1 and alpha PS2 integrins of Drosophila melanogaster, and each family has duplicated repeatedly in vertebrates but not in Drosophila. In contrast, a third family (including alpha PS3) has duplicated in Drosophila but is absent from vertebrates. Vertebrate alpha PS1 and alpha PS2 family members are found on human chromosomes 2, 12, and 17. Linkage of these family members may have been conserved since prior to the origin of vertebrates, and the two genes duplicated simultaneously. A phylogenetic analysis of beta integrins did not clearly resolve whether vertebrate beta integrin genes duplicated prior to the origin of vertebrates, although it suggested that at least the gene encoding vertebrate beta 4 may have done so. In general, the phylogeny of neither alpha nor beta integrins showed a close correspondence with patterns of alpha--beta heterodimer formation or other functional characteristics. One major exception to this trend involved alpha L, alpha M, alpha X, and alpha D, a monophyletic group of immune cell-expressed alpha integrins, which share a number of common functional characteristics and have evolved in coordinated fashion with their beta integrin partners.

Animals↗

PubMed2003

Scatter factor regulation of integrin expression and function on oral epithelial cells.

Integrin receptors and the growth factor, scatter factor (SF; also known as hepatocyte growth factor) have been shown to modulate similar cellular processes including embryogenesis, wound healing and tumour invasion. The purpose of this study was to examine the role of SF in the regulation of integrin expression, migration and adhesion in normal human oral keratinocytes (NHK). Integrin expression was examined using flow cytometry, SF did not alter levels of expression but had a dramatic effect on cell morphology, inducing migratory filopodia and lamellipodia. SF selectively induced migration towards fibronectin, but not towards collagen I. Integrin function was further investigated by measuring the ability of NHK to adhere and migrate on various integrin ligands. SF reduced adhesion of NHK to collagen types I and IV, laminins 1 and 5 and fibronectin. The inclusion of function-blocking antibodies revealed that SF mediated upregulation of migration through alpha(5)beta(1) integrin and downregulation of adhesion through alpha(v) integrins. SF increased tyrosine phosphorylation of FAK protein in NHK after a 30-min treatment. These results show that SF can affect keratinocyte behaviour by modifying integrin function but not expression.

Antibodies↗

PubMed2005

Integrin expression in developing human salivary glands.

The development and complete differentiation of salivary glands is a complex process that involves a large number of co-ordinated events. Little is known about the molecular basis for salivary gland development. However, we have reported previously that integrins appear to play a role. Integrins are heterodimeric transmembrane receptors consisting of one alpha and one beta subunit that play a pivotal role in the interaction of cells with the extracellular matrix. Such interactions regulate the organisation of cells of tissues and organs during development as well as cell proliferation and differentiation. Using immunohistochemistry and Western and Northern blot analysis, we mapped the localisation and expression of integrins beta1, beta3 and beta4 in human salivary glands obtained from foetuses ranging from weeks 4-24 of gestation and compared it with adult salivary glands. Integrin beta1 first appeared during the canalisation stage and during the differentiation stage. A message first appeared at week 6 of development. The expression of beta4 integrin protein and message was observed only in the late stage of differentiation. Integrin beta3 was not detected in the developing glands; however, integrins beta1, beta3 and beta4 were all expressed in adult salivary gland tissues. The data suggest that integrins, particularly beta1, have a role to play in salivary gland development and differentiation.

Adult↗

PubMed2004

Effect of suture repair on expression of beta1 integrin subunit in wounded rat patellar tendon.

Integrins play key roles in wound healing by mediating cell adhesion events. The purpose of this study was to determine how to change the expression level of the beta1 integrin subunit (integrin beta1) in the restoration of a tendon and to investigate the influence of suture on its expression. The lateral half of the patellar tendon in rats was transected. Half the rats were sutured immediately and the other half were left as they were. The rats were killed at 4, 7, 10, 14, 28, and 56 days postsurgery. Integrin beta1 expression in each harvested tendon was analyzed using immunohistochemistry and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Integrin beta1 was immunolocalized in fibroblasts adjacent to the wound and within the repair site itself. Although immunoreactivity for integrin beta1 in the unsutured group decreased on the tenth day, that in the sutured group continued to increase. In real-time quantitative RT-PCR, integrin beta1 mRNA expression level increased in both groups, but that in the unsutured group was higher than that in the sutured group. Our study indicates that suture influences the expression and mRNA level of integrin beta1, which is associated with tendon healing.

Animals↗

PubMed2006

HOXD3-overexpression increases integrin alpha v beta 3 expression and deprives E-cadherin while it enhances cell motility in A549 cells.

We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin beta3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin beta3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays. The integrin beta3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin alphav subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectants > the integrin beta3-transfectants > the control transfectants or parental cells. E-cadherin was expressed in the integrin beta3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin beta3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin alphav beta3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.

Animals↗

PubMed2006

Crosstalk between hepatocyte growth factor and integrin signaling pathways.

Most types of normal cells require integrin-mediated attachment to extracellular matrix to be able to respond to growth factor stimulation for proliferation and survival. Therefore, a consensus that integrins are close collaborators with growth factors in signal transduction has gradually emerged. Some integrins and growth factor receptors appear to be normally in relatively close proximity, which can be induced to form complexes upon cell adhesion or growth factor stimulation. Moreover, since integrins and growth factor receptors share many common elements in their signaling pathways, it is clear tzhat there are many opportunities for integrin signals to modulate growth factor signals and vice versa. Increasing evidence indicates that integrins can crosstalk with receptor tyrosine kinases in a cell- and integrin-type-dependent manner through a variety of specific mechanisms. This review is intended specifically for summarizing recent progress uncovering how the hepatocyte growth factor receptor c-Met coordinates with integrins to transmit signals.

Animals↗

PubMed1992

Beta 1 and beta 3 integrins have different roles in the adhesion and migration of vascular smooth muscle cells on extracellular matrix.

Extracellular matrix receptors on ductus arteriosus smooth muscle cells (SMC) must enable the cells to migrate through both interstitial and basement membrane matrices to form intimal mounds during postnatal ductus closure. We examined the role of beta 1 and beta 3 integrin receptors on SMC adhesion and migration. Using a new assay to measure cell migration, we found that lamb ductus arteriosus SMC attach to and migrate over surfaces coated with fibronectin (FN), laminin (LN), vitronectin (VN), and collagens I (I) and IV (IV). Blocking antibodies, specific to different integrin complexes, showed that SMC adhesion to FN, LN, I, and IV depended exclusively on functioning beta 1 integrins with little, if any, contribution by the alpha V beta 3 integrin; on the other hand, cell migration over these substrates depended to a large extent on the alpha V beta 3 receptor. Immunofluorescent staining demonstrated that during the early phase of SMC migration, the beta 1 integrins organized rapidly into focal plaques that, with time, gradually covered the cell's basal surface; on the other hand, the beta 3 receptor remained concentrated at all times at the cell's margins. Ligand affinity chromatography and immunoprecipitation techniques identified a unique series of beta 1 integrins binding to each matrix component: FN (alpha 5 beta 1, alpha 3 beta 1, alpha V beta 1), LN (alpha 1 beta 1, alpha 7 beta 1), VN (alpha V beta 1), I (alpha 1 beta 1, alpha 2 beta 1), and IV (alpha 1 beta 1). In contrast, the beta 3 integrin, alpha V beta 3, bound to all the substrates tested: FN, LN, VN, I, and IV. The results indicate that beta 1 and beta 3 integrins may play different roles in attachment and migration as SMC move through the vascular extracellular matrix to produce obliteration of the ductus arteriosus lumen.

Amino Acid Sequence↗

PubMed1994

Altered interaction of human granulation-tissue fibroblasts with fibronectin is regulated by alpha 5 beta 1 integrin.

Granulation-tissue fibroblasts express an unique phenotype distinct from normal fibroblasts. Due to the importance of the cell-matrix interactions in the regulation of cell morphology and behavior, we have compared the cell adhesion apparatus, especially integrin-type receptors, in fibroblasts cultured from healthy human periodontal connective tissues and from chronic and wound granulation tissues. The spreading of granulation-tissue cells on fibronectin, but not on type I collagen or laminin, was slower when compared with the normal fibroblasts. Cell spreading on fibronectin could be inhibited by RGD-containing peptide, suggesting integrin-mediated interaction. Both cell types expressed beta 1 integrin subunit, which associated with several integrin alpha subunits, namely alpha 1, alpha 2, alpha 3, alpha 5 and alpha v. In addition to beta 1 subunit, alpha v chain formed heterodimers with beta 3 and beta 5 subunits. Thus, these cells have multiple putative fibronectin, laminin, collagen, and vitronectin receptors. Cell spreading of both cell types on fibronectin was inhibited with anti-beta 1 and anti-alpha 5 antibodies, but antibodies against other putative FN-binding integrins (alpha 3, alpha v, and alpha v beta 3) had no effects. Furthermore, granulation-tissue fibroblasts showed delayed spreading on substrates coated with anti-beta 1 or anti-alpha 5 integrin antibodies. On substrates coated with anti-alpha 3 antibody, both cell types spread equally well. By FACS analysis, the amount of beta 1 and alpha 5 integrin subunits expressed on the cell surfaces was slightly elevated in GTFs compared with HGFs. Thus, the findings in this study indicate that the weakened interaction of granulation-tissue fibroblasts with fibronectin is regulated by altered function of alpha 5 beta 1 integrin.

Amino Acid Sequence↗

PubMed1995

Cell migration: interactions among integrins, IGFs and IGFBPs.

The migratory behaviour of cells is fundamental to diverse biologic processes such as tumor metastasis, development of atherosclerotic plaques, embryonic development and wound healing. We have examined the effects of IGF-I and IGFBPs on the migration of Chinese Hamster ovary (CHO) cells, smooth muscle cells (SMC) and human breast cancer cells (HBC) and have studied the involvement of integrin receptors in migration induced by IGF-I and by IGFBPs. Using a monolayer wounding assay, we determined the effect of IGFBP-1 on SMC to be qualitatively similar to its effect we reported earlier on CHO cells, in that there is a direct stimulation of migration mediated by the alpha 5 beta 1 integrin. IGFBP-2 has no direct effect on SMC migration, and although it also contains the Arg-Gly-Asp sequence, we can detect no integrin binding. Unlike CHO cells, SMC are stimulated to migrate by IGF-I. IGFBP-2 and IGFBP-1 both inhibit this IGF-I receptor-mediated stimulation. We have also studied the migration of HBC using a Boyden chamber apparatus and have shown a potent chemotactic effect of IGF-I. We have investigated the mechanisms for IGF-I stimulation of SMC and HBC migration. IGF-I stimulation of SMC migration requires the presence of either 0.2% serum or vitronectin, because of a requirement for ligand binding by the alpha V beta 3 integrin (vitronectin receptor). MCF-7 HBC migrate toward a concentration gradient of IGF-I, the only growth factor that was able to stimulate these cells to migrate. Integrin ligand binding was also necessary for MCF-7 cells to migrate in response to IGF-I; alpha V beta 5 integrin was required for migration on vitronectin and alpha 2 beta 1 was required on collagen. These studies demonstrate that the stimulation of cell migration by IGFBP-1 and IGF-I involves signaling by members of the integrin family of receptors. The mechanisms by which the IGF-I receptor and integrin receptors interact are not yet known.

Animals↗

PubMed2006

Integrin engagement modulates the phosphorylation of focal adhesion kinase, phagocytosis, and cell spreading in molluscan defence cells.

Integrins play a key role in cellular immune responses in a variety of organisms; however, knowledge of integrins and their effects on cell signalling and functional responses in molluscan defence reactions is poor. Using integrin-mediated cell adhesion kits, alphaVbeta3 and beta1 integrin-like subunits were identified on the surface of Lymnaea stagnalis haemocytes. Haemocyte binding via these integrins was found to be dependent on Ca2+/Mg2+. Western blotting with an anti-phospho (anti-active) focal adhesion kinase (FAK) antibody revealed a 120-125 kDa FAK-like protein in these cells; this protein was transiently phosphorylated upon haemocyte adhesion over 90 min, with maximal phosphorylation occurring after 30 min binding. Also, integrin engagement with the tetrapeptide Arg-Gly-Asp-Ser (RGDS) resulted in a rapid increase in phosphorylation of the FAK-like protein; however, RGDS did not affect the phosphorylation of extracellular signal-regulated kinase. Treatment of haemocytes with RGDS (2 mM) inhibited phagocytosis of E. coli bioparticles by 88%. Moreover, at this concentration, RGDS reduced cell spreading by 61%; stress fiber formation was also impaired. Taken together, these results demonstrate a role for integrins in L. stagnalis haemocyte adhesion and defence reactions and, for the first time, link integrin engagement to FAK activation in molluscs.

Animals↗

PubMed2005

Cellular entry of Hantaan virus A9 strain: specific interactions with beta3 integrins and a novel 70kDa protein.

Cellular entry of pathogenic hantaviruses had been shown to be mediated by beta3 integrins. However, no direct evidence exists that hantavirus binds to beta3 integrins, and integrin beta3 subunit is not expressed on some cells permissive to hantavirus infection. In this report, utilizing beta3-integrin-transfected CHO cells, we demonstrated that integrin beta3 subunit renders CHO cells susceptible to Chinese Hantaan virus (HTN) strain A9 (isolated in China), and the viral infection was correspondingly inhibited by antibodies to alphavbeta3, alphaIIbbeta3, beta3, and alphav integrins. Furthermore, virus overlay protein-binding assay and 'quarternary Western' analysis indicate that HTN A9 directly interacts with beta3 integrins and an unidentified 70kDa protein. These findings indicate that beta3 integrins play a crucial role in cellular entry of HTN A9 via specific interactions with the virus. In addition, a novel 70kDa protein may serves as a candidate receptor or alternative cellular component for interaction with HTN.

Animals↗