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PubMed2003

Recognition of novel viral sequences that associate with the dynein light chain LC8 identified through a pepscan technique.

Recent data from multiple laboratories indicate that upon infection, many different families of viruses hijack the dynein motor machinery and become transported in a retrograde manner towards the cell nucleus. In certain cases, one of the dynein light chains, LC8, is involved in this interaction. Using a library of overlapping dodecapeptides synthesized on a cellulose membrane (pepscan technique) we have analyzed the interaction of the dynein light chain LC8 with 17 polypeptides of viral origin. We demonstrate the strong binding of two herpesvirus polypeptides, the human adenovirus protease, vaccinia virus polymerase, human papillomavirus E4 protein, yam mosaic virus polyprotein, human respiratory syncytial virus attachment glycoprotein, human coxsackievirus capsid protein and the product of the AMV179 gene of an insect poxvirus to LC8. Our data corroborate the manipulation of the dynein macromolecular complex of the cell during viral infection and point towards the light chain LC8 as one of the most frequently used targets of virus manipulation.

Adenoviridae↗
PubMed2004

Targeting DNA with novel diphenylcarbazoles.

Double-stranded DNA is a therapeutic target for a variety of anticancer and antimicrobial drugs. Noncovalent interactions of small molecules with DNA usually occur via intercalation of planar compounds between adjacent base pairs or minor-groove recognition by extended crescent-shaped ligands. However, the dynamic and flexibility of the DNA platform provide a variety of conformations that can be targeted by structurally diverse compounds. Here, we propose a novel DNA-binding template for construction of new therapeutic candidates. Four bisphenylcarbazole derivatives, derived from the combined molecular architectures of known antitumor bisphenylbenzimidazoles and anti-infectious dicationic carbazoles, have been designed, and their interaction with DNA has been studied by a combination of biochemical and biophysical methods. The substitutions of the bisphenylcarbazole core with two terminal dimethylaminoalkoxy side chains strongly promote the interaction with DNA, to prevent the heat denaturation of the double helix. The deletion or the replacement of the dimethylamino-terminal groups with hydroxyl groups strongly decreased DNA interaction, and the addition of a third cationic side chain on the carbazole nitrogen reinforced the affinity of the compound for DNA. Although the bi- and tridentate molecules both derive from well-characterized DNA minor-groove binders, the analysis of their binding mode by means of circular and linear dichroism methods suggests that these compounds form intercalation complexes with DNA. Negative-reduced dichroism signals were recorded in the presence of natural DNA and synthetic AT and GC polynucleotides. The intercalation hypothesis was validated by unwinding experiments using topoisomerase I. Prominent gel shifts were observed with the di- and trisubstituted bisphenylcarbazoles but not with the uncharged analogues. These observations, together with the documented stacking properties of such molecules (components for liquid crystals), prompted us to investigate their binding to the human telomeric DNA sequence by means of biosensor surface plasmon resonance. Under conditions favorable to G4 formation, the title compounds showed only a modest interaction with the telomeric quadruplex sequence, comparable to that measured with a double-stranded oligonucleotide. Their sequence preference was explored by DNase I footprinting experiments from which we identified a composite set of binding sequences comprising short AT stretches and a few other mixed AT/GC blocks with no special AT character. The variety of the binding sequences possibly reflects the coexistence of distinct positioning of the chromophore in the intercalation sites. The bisphenylcarbazole unit represents an original pharmacophore for DNA recognition. Its branched structure, with two or three arms suitable to introduce a structural diversity, provides an interesting scaffold to built molecules susceptible to discriminate between the different conformations of nucleic acids.

Base Sequence↗
PubMed1994

Heubner's artery variations in anterior communicating artery aneurysms.

This study attempts to analyse the intra-operative anatomical findings of the recurrent artery of Heubner in 48 patients with Anterior Communicating Artery Aneurysm who were operated on at the Neurosurgical Department of Atatürk University Medical School, Erzurum, Türkiye. All patients underwent radical surgery for aneurysm by the right pterional approach. The findings were recorded during surgical intervention and through the dias and videotapes of the operations. The artery of Heubner originated from the junction of the A1 and A2 segments of the anterior cerebral artery (ACA) in 58%, from the A2 segment of ACA in 23%, and from the A1 segment of ACA 4%. It was asymmetrically taking off in 13% and hypoplastic in 2% of the cases. Three types of recurrent artery courses were defined. The type I or the superior course was seen in 71%, the type II or the anterior course was found in 25% and type III or the posterior course was recorded in 4% of patients. We concluded that the recognition of the anatomical variations of the recurrent artery of Heubner and the detailed knowledge of the microvascular relationships of the anterior communicating artery (ACoA) complex, will allow neurosurgeons to construct a better and safer microdissection plan, to save time, and so prevent postoperative neurological deficit.

Adolescent↗
PubMed1992

T-cell receptor gamma delta-positive peripheral T-cell lymphomas presenting in the skin: a clinical, histological and immunophenotypic study.

Examination of biopsy samples from 62 patients with--or with suspected--cutaneous T-cell lymphoma (CTCL) revealed 2 cases in which the neoplastic cells were positive for the T-cell receptor (TCR) gamma delta complex. One patient had mycosis fungoides and 1 patient had a pleomorphic lymphoma of medium and large-cell type. Both cases showed aggressive courses with dissemination to internal organs and short survival times. The phenotypic examination showed that the neoplastic cells were positive with TCR delta 1, CD3, CD25, CD29, CD45R0 and CD54. No staining was seen with antibodies against framework determinants or variable regions on the TCR alpha beta heterodimer. Negative reactions were also seen with CD4, CD8, CD5, CD7, CD16, CD30 and CD57. It is concluded that rare CTCL express TCR gamma delta chains. These malignancies may originate from the TCR gamma delta-positive T cells seen in normal skin, and it is possible that their recognition may be important for clinical reasons.

Female↗
PubMed1987

The subclass heterogeneity of pig IgG.

The recognition and distinction of pig IgG subclasses is a difficult task because no pathological monoclonal immunoglobulins of pig origin are available. Attempts at elucidating the subclass composition of pig IgG based on subfractionation of pooled IgG and preparation of antisera has led to only partial success. Chemical evidence for heterogeneity of the constant portion of pig gamma-chains pointed to the existence of more than one subclass; a final answer to the question of the number of subclasses could not be obtained. Functionally different antibodies of the IgG class may be isolated from immune sera collected at various stages of the immune response. Precipitating and nonprecipitating anti-dinitro-phenyl (DNP) antibodies differ chiefly in their capacity for forming insoluble complexes with DNP-carrier proteins. Examination of these antibodies by physical methods showed that the precipitating antibody is less compact, more flexible and that the distance between the two binding sites on the same molecule are greater than for the nonprecipitating anti-DNP antibody. The precipitating antibody is very resistant to cleavage by pepsin compared to the non-precipitating antibody. This resistance, together with the differences in the molecular parameters described above provides evidence that precipitating and nonprecipitating anti-DNP antibodies in swine are representatives of separate IgG subclasses. Mouse monoclonal antibodies to pig IgG show a degree of selectivity for certain IgG subpopulations when tested against pooled pig IgG. The limited number of monoclonal antibodies currently available does not allow final conclusions to be drawn on the number of pig IgG subclasses.

Amino Acid Sequence↗
PubMed2005

The influence of environment on development of the mucosal immune system.

The mucosal immune system expresses active responses against pathogens and also tolerance against harmless food and commensal bacterial antigens. The mechanisms that determine which of these outcomes occur after recognition of antigens by T-cells are not clear. One possibility is that it is determined by the initial interaction between a dendritic and a naïve T-cell in organised lymphoid tissue. However, such organised structures are, evolutionarily, quite recent and the original immune system must have made appropriate responses in more diffuse immunological architecture; a second possibility is that the critical interaction is between primed T-cells and their environment, in the lamina propria of the intestine. The mucosal immune system of neonates is poorly developed and inefficient at expressing appropriate immune responses. Development is influenced by a range of environmental factors including maternally derived antigen or antibody and commensal flora and pathogens. The intestine is a complex immunological structure in which the immune system and the macro- and microenvironment interact.

Animals↗
PubMed2003

Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy.

OBJECTIVES: The goal of this study was to determine the impact of race on identification of hypertrophic cardiomyopathy (HCM). BACKGROUND: Sudden death in young competitive athletes is due to a variety of cardiovascular diseases (CVDs) and, most commonly, HCM. These catastrophes have become an important issue for African Americans, although HCM has been previously regarded as rare in this segment of the U.S. population. METHODS: We studied the relationship of race to the prevalence of CVDs causing sudden death in our national athlete registry, and compared these findings with a representative multicenter hospital-based cohort of patients with HCM. RESULTS: Of 584 athlete deaths, 286 were documented to be due to CVD at ages 17 +/- 3 years; 156 (55%) were white, and 120 (42%) were African American. Most were male (90%), and 67% participated in basketball and football. Among the 286 cardiovascular deaths, most were due to HCM (n = 102; 36%) or anomalous coronary artery of wrong sinus origin (n = 37; 13%). Of the athletes who died of HCM, 42 (41%) were white, but 56 (55%) were African American. In contrast, of 1,986 clinically identified HCM patients, only 158 (8%) were African American (p < 0.001). CONCLUSIONS: In this autopsy series, HCM represented a common cause of sudden death in young and previously undiagnosed African American male athletes, in sharp contrast with the infrequent clinical identification of HCM in a hospital-based population (i.e., by seven-fold). This discrepancy suggests that many HCM cases go unrecognized in the African American community, underscoring the need for enhanced clinical recognition of HCM to create the opportunity for preventive measures to be employed in high-risk patients with this complex disease.

Adolescent↗
PubMed2004

The role of the substantia nigra in cognitive activity in cats.

The role of the substantia nigra in cognitive processes of different levels of complexity was studied using an original method. Neurosurgical or neurochemical exclusion of the substantia nigra in cats led to significant impairment of conditioned reflex activity, generalization and abstraction processes; these recovered with pharmacological treatment directed to the dopaminergic system, with partial recovery after treatment directed to the GABAergic and cholinergic systems. Treatment directed to the serotoninergic system was ineffective.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Molecular structures and functions of pyocins S1 and S2 in Pseudomonas aeruginosa.

Pyocins S1 and S2 are S-type bacteriocins of Pseudomonas aeruginosa with different receptor recognition specificities. The genetic determinants of these pyocins have been cloned from the chromosomes of P. aeruginosa NIH-H and PAO, respectively. Each determinant constitutes an operon encoding two proteins of molecular weights 65,600 and 10,000 (pyocin S1) or 74,000 and 10,000 (pyocin S2) with a characteristic sequence (P box), a possible regulatory element involved in the induction of pyocin production, in the 5' upstream region. These pyocins have almost identical primary sequences; only the amino-terminal portions of the large proteins are substantially different. The sequence homology suggests that pyocins S1 and S2, like pyocin AP41, originated from a common ancestor of the E2 group colicins. Purified pyocins S1 and S2 make up a complex of the two proteins. Both pyocins cause breakdown of chromosomal DNA as well as complete inhibition of lipid synthesis in sensitive cells. The large protein, but not the pyocin complex, shows in vitro DNase activity. This activity is inhibited by the small protein of either pyocin. Putative domain structures of these pyocins and their killing mechanism are discussed.

Amino Acid Sequence↗
PubMed1999

The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation.

T cells constantly sample their environment using receptors (TCR) that possess both a germline-encoded low affinity for major histocompatibility complex (MHC) molecules and a highly diverse set of CDR3 regions contributing to a range of affinities for specific peptides bound to these MHC molecules. The decision of a T cell "to sense and to respond" with proliferation and effector activity rather than "to sense, live on, but not respond" is dependent on TCR interaction with a low number of specific foreign peptide:MHC molecule complexes recognized simultaneously with abundant self peptide-containing complexes. Interaction with self-complexes alone, on the other hand, generates a signal for survival without a full activation response. Current models for how this distinction is achieved are largely based on translating differences in receptor affinity for foreign versus self ligands into intracellular signals that differ in quality, intensity, and/or duration. A variety of rate-dependent mechanisms involving assembly of molecular oligomers and enzymatic modification of proteins underlie this differential signaling. Recent advances have been made in measuring TCR:ligand interactions, in understanding the biochemical origin of distinct proximal and distal signaling events resulting from TCR binding to various ligands, and in appreciating the role of feedback pathways. This new information can be synthesized into a model of how self and foreign ligand recognition each evoke the proper responses from T cells, how these two classes of signaling events interact, and how pathologic responses may arise as a result of the underlying properties of the system. The principles of signal spreading and stochastic resonance incorporated into this model reveal a striking similarity in mechanisms of decision-making among T cells, neurons, and bacteria.

Animals↗
PubMed2004

The achilles heel of ErbB-2/HER2: regulation by the Hsp90 chaperone machine and potential for pharmacological intervention.

Signal transduction mediated by ErbB/HER receptor tyrosine kinases is crucial for the development and maintenance of epithelial tissues, and aberrant signaling is frequently associated with malignancies of epithelial origin. This review focuses on the roles played by the Hsp90 chaperone machinery in the regulation of signaling through the ErbB/HER network, and discusses potential therapeutic strategies that disrupt chaperone functions. Hsp90 and its associated cochaperones regulate ErbB signal transduction through multiple mechanisms. The chaperone system controls the stability of the nascent forms of both ErbB-1 (EGF-receptor) and ErbB-2/HER2, while regulation of the mature form is restricted to ErbB-2. Regulation by the Hsp90 complex extends to downstream effectors of ErbB signaling, namely Raf-1, Pdk-1 and Akt/PKB. Disrupting the function of Hsp90 results in the degradation of both the receptors and their effectors, thereby inhibiting tumor cell growth. The importance of an Hsp90-recognition motif located within the kinase domain of ErbB-2 is discussed, as well as a direct role for Hsp90 in regulating tyrosine kinase activity. In light of recent observations, we emphasize the ability of specific tyrosine kinase inhibitors to selectively target ErbB-2 to the chaperone-mediated degradation pathway. ErbB-specific drugs are already used to treat cancers, and clinical trials are underway for additional compounds that intercept ErbB signaling, including drugs that target Hsp90. Hence, the dependence of ErbB-2 upon Hsp90 reveals an Achilles heel, which opens a window of opportunity for combating cancers driven by the ErbB/HER signaling network.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1994

V beta 5+ T cell receptors skew toward OVA+H-2Kb recognition.

T cells recognize a complex of peptide Ag bound within the groove of MHC-encoded molecules. Although many studies have attempted to correlate TCR gene expression with specificity for particular Ag/MHC combinations, it is still not clear exactly how the TCR physically interacts with its cognate ligand. We have analyzed transgenic mice that carry a rearranged gene encoding a V beta 5.2+ TCR beta-chain derived from the CD8+ CTL clone B3, which is specific for chicken OVA+H-2Kb. Surprisingly, we have found that peripheral lymphocytes isolated from naïve V beta 5.2 transgenic mice can generate a strong primary anti-OVA CTL response when stimulated in vitro with OVA+H-2b, whereas generation of even a weak anti-OVA response from nontransgenic littermates requires in vivo priming. This response is Ag specific, because the transgenic mice are unable to respond with or without priming to vesicular stomatitis virus, which contains a dominant epitope presented in the context of H-2Kb. The precursor frequency of OVA-specific CTL in unprimed V beta 5.2 transgenic mice is approximately 30-fold higher than that in nontransgenic littermate controls. Reverse transcription-PCR analyses demonstrate that OVA-specific CTL lines derived from unprimed V beta 5.2 transgenic mice express a variety of TCR V alpha elements, indicating that the transgenic anti-OVA response is not solely due to the reconstitution of the original B3 TCR. In fact, our data suggest that even a nontransgenic V beta 5+ TCR is intrinsically OVA specific. First, five separate OVA-specific oligoclonal CTL lines derived from individual nontransgenic mice demonstrate dramatic skewing toward expression of V beta 5.1+ or V beta 5.2+ TCR over the course of several in vitro stimulations. Second, sorting for V beta 5+CD8+ nontransgenic cells enriches for OVA-specific CTL. However, peptide antagonism experiments using mutant forms of the Kb-restricted OVA peptide reveal distinct differences between the recognition patterns of two individual OVA-specific CTL lines derived from unprimed V beta 5.2 transgenic mice. These experiments support the notion that a discrete portion of the responding TCR can heavily influence but not necessarily be solely sufficient for the recognition of a peptide Ag presented in the cleft of an MHC-encoded molecule.

Amino Acid Sequence↗
PubMed1993

Positive selection of T lymphocytes on fibroblasts.

Thymocytes are selected for expression of alpha beta T-cell antigen receptors (TCR) which recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. In the thymus the restriction element is imprinted on radioresistant stromal elements and on cells of haematopoietic origin. In mice negative for beta 2-microglobulin that are devoid of mature cytotoxic T lymphocytes, we find that intrathymic injection of different fibroblasts causes the maturation of CD4-CD8+TCRhigh thymocytes with distinct patterns of TCR V beta distribution. Here we show that in TCR-transgenic mice, intrathymic injection of L cells expressing the selecting H-2Kb molecule (L-Kb cells) reconstitutes the maturation of thymocytes bearing the transgenic TCR, and that in normal B10.BR (H-2k) mice, H-2Kb molecules expressed on L-Kb cells lead to the development of T lymphocytes with recognition restricted to H-2Kb. A class I MHC restriction element can thus be selected by interaction with fibroblasts, that is, cells of other than epithelial or haematopoietic origin.

Animals↗
PubMed2003

A PDZ domain-based assay for measuring HIV protease activity: assay design considerations.

We have recently described a biochemical detection method for peptide products of enzymatic reactions based on the formation of PDZ domain*peptide ligand complexes. The product sensor is based on using masked or cryptic PDZ domain peptide ligands as enzyme substrates. Upon enzymatic processing, a PDZ-binding motif is exposed, and the product sequence bound specifically by a Eu(3+)chelate-labeled GST-PDZ ([Eu(3+)]GST-PDZ). The practical applicability of this PDZ-based detection method is determined by the affinity of the PDZ domain*peptide ligand interaction, and the efficiency of the enzyme to process the masked peptide ligand. To expand the use of this PDZ-based detection strategy to a broader range of enzymatic assays, we have taken advantage of the plasticity in ligand recognition by the variety of PDZ domains found in nature. In the original work, the PDZ3 of PSD-95 was used, which preferentially recognizes the consensus sequence Ser-X-Val-COOH. Here, we show that NHERF PDZ1, which binds to the consensus sequence Thr/Ser-X-Leu-COOH, can be used to extend the flexibility in the recognition of the carboxy-terminal amino acid of the ligand, and monitor the enzymatic activity of HIV protease. The choices of detection format, for example, TRET or ALPHA, were also investigated and influenced assay design.

DNA Primers↗
PubMedDate not supplied

Memory function and verbal learning ability in patients with complex partial seizures of temporal lobe origin.

A variety of experimental paradigms have been utilized to study verbal learning and memory ability in patients with epilepsy. One commonly used paradigm, the free recall of a list(s) of related or unrelated words, has revealed a variety of performance anomalies in patients with complex partial seizures (CPS) of temporal lobe origin, but published studies have varied markedly in important methodological details, making it difficult to interpret discrepant findings as well as to assess the generalizability of results. The purpose of this investigation was to simultaneously inquire into several aspects of verbal learning and memory function that have been reported or hypothesized to be compromised in individuals with CPS of left temporal lobe origin. Thirty patients with CPS of lateralized temporal lobe onset [15 left temporal (LT) and 15 right temporal (RT)] were compared with 15 matched controls (NC) on several measures derived from the California Verbal Learning Test (CVLT), i.e., verbal learning ability, immediate free recall, presence of retroactive interference effects, semantic organization, retrieval efficiency, and recognition memory. Compared to RT and NC groups, the LT patients manifested poorer verbal learning ability, impaired immediate memory, and increased difficulty in the retrieval of verbal material from memory store. Compared to NC subjects, the LT group showed poorer semantic organization in their verbal learning and recall. The RT and NC groups were essentially similar in all respects. Finally, the clinical utility of these findings were investigated, and a series of decision rules designed to separate LT from RT patients was derived.

Epilepsy, Temporal Lobe↗
PubMed1987

CAMs and Igs: cell adhesion and the evolutionary origins of immunity.

The lymphoid system and cells of immunity are as morphologically well defined as those of any complex organ but in addition they show dynamic long-range interactions between the fluid tissues (lymphocytes, monocytes, etc.) and the solid, vascular and generative tissues and organs which they comprise. Given the observation that CAMs are present in epithelial components of lymphoid organs, it appears that, in their ontogeny, the organs of immunity will share a common principle of morphoregulation by CAMs with brains, feathers and other parts of the phenotype. As discussed here, this principle is a regulatory one operating across many levels of organization from the genes to tissues and back again (see Fig. 1). At some early point in the evolution of the immune system, a gene corresponding to an N-CAM precursor must have duplicated to provide a basis for the Ig superfamily with its increasing specializations for recognition and for cellular regulation during the immune response. Lymphocyte cellular families also developed later specializations (along with other leukocytes) for adhesive functions accessory to specific recognition. As far as we can see, the molecules for these accessory functions only remotely resemble CAMs, but closely resemble receptors for matrix molecules and SAMs. What CAMs and Ig superfamily members have in common is an evolutionary path and important roles in mediating complex regulatory responses that arise from cell-cell interactions. In the one case, this regulation leads to morphology, and in the other, to immune recognition. The first depends directly upon pattern (the formation of definite tissue structure); the regulation of the second also depends upon pattern to the extent that its function is dependent upon the morphology of lymphoid organs and vasculature. But although specific immune recognition depends locally upon adhesion through special mechanisms, it does not lead to morphology. One must not therefore impute too much in the physiological sense to the resemblance among brain molecules and molecules of the immune system. CAMs themselves are not directly histotypic at the level of individual differentiated cells but rather are used to link early tissue boundaries in induction and function in a wide variety of different tissues. As a consequence, N-CAM is central to the formation and maintenance of neural tissue but has a much wider tissue distribution and a fundamental role in very early embryogenesis as is the case with other primary CAMs. Thus, the immune system did not evolve from the nervous system, but from a cell adhesion system essential to both.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Human allospecific TLCs generated against HLA antigens associated with DR1 through DRw8. II. Population analyses and blocking studies with monoclonal antibodies.

Serologic, cellular, and molecular evidence supports the concept of extreme complexity within the HLA-D region. To study the complexity and fine specificity of the HLA-D region at the level of T-cell recognition, a panel of T-cell clones was generated against alloantigens associated with HLA-DR1 through -DRw8. After initial screening of more than 800 clones, 89 representative lines were selected for extensive testing against 204 unrelated stimulator cells. Clone-by-clone correlation analyses were performed to test whether any clones recognized similar or identical epitopes. In addition, clonal reactivity patterns were correlated with known HLA specificities. Twelve clusters of clones were identified with similar reactivity patterns using clone-by-clone correlation analysis. Some groups were significantly correlated with specificities associated with various D-region haplotypes; others had no significant correlation with any defined D-region specificity. Five general types of clones obtained in our study can be categorized as follows: Those recognizing epitopes clearly demonstrating a primary association with the classically defined D-region molecules against which the clones were primed. Clones recognizing epitopes associated with one of the priming antigens and also with another unrelated D-region specificity. Clones detecting epitopes which showed significant correlation with D-region molecules totally different from those against which they were originally primed. Clones with limited reactivity in population studies and no correlation with defined D-region molecules. Clones recognizing class I-associated epitopes.

Antibodies, Monoclonal↗
PubMed1994

Viral cell recognition and entry.

Rhinovirus infection is initiated by the recognition of a specific cell-surface receptor. The major group of rhinovirus serotypes attach to intercellular adhesion molecule-1 (ICAM-1). The attachment process initiates a series of conformational changes resulting in the loss of genomic RNA from the virion. X-ray crystallography and sequence comparisons suggested that a deep crevice or canyon is the site on the virus recognized by the cellular receptor molecule. This has now been verified by electron microscopy of human rhinovirus 14 (HRV14) and HRV16 complexed with a soluble component of ICAM-1. A hydrophobic pocket underneath the canyon is the site of binding of various hydrophobic drug compounds that can inhibit attachment and uncoating. This pocket is also associated with an unidentified, possibly cellular in origin, "pocket factor." The pocket factor binding site overlaps the binding site of the receptor. It is suggested that competition between the pocket factor and receptor regulates the conformational changes required for the initiation of the entry of the genomic RNA into the cell.

Intercellular Adhesion Molecule-1↗