Nucleolin-RNA interaction modulates rotavirus replication.

Rotavirus infection is a leading cause of gastroenteritis in children worldwide; the genome of this virus is composed of 11 segments of dsRNA packed in a triple-layered protein capsid. Here, we investigated the role of nucleolin, a protein with diverse RNA-binding domains, in rotavirus infection. Knocking down the expression of nucleolin in MA104 cells by RNA interference resulted in a remarkable 6.3-fold increase in the production of infectious rhesus rotavirus (RRV) progeny, accompanied by an elevated synthesis of viral mRNA and genome copies. Further analysis unveiled an interaction between rotavirus segment 10 (S10) and nucleolin, potentially mediated by G-quadruplex domains on the viral genome. To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA-binding domains. Under these conditions, viral production increased by 1.5-fold, indicating the inhibitory role of nucleolin on the yield of infectious viral particles. Furthermore, G4 sequences were identified in all 11 RRV dsRNA segments, and transfection of oligonucleotides representing G4 sequences in RRV S10 induced a significant increase in viral production. These findings show that rotavirus replication is negatively regulated by nucleolin through the direct interaction with the viral RNAs by sequences forming G4 structures.IMPORTANCEViruses rely on cellular proteins to carry out their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.

Nucleation and growth of gold nanoparticles in the presence of different surfactants. A dissipative particle dynamics study.

Nanoparticles (NPs) show promising applications in biomedicine, catalysis, and energy harvesting. This applicability relies on controlling the material's features at the nanometer scale. Surfactants, a unique class of surface-active molecules, have a remarkable ability to tune NPs activity; provide specific functions, avoid their aggregation, and create stable colloidal solutions. Surfactants also control nanoparticles' nucleation and growth processes by modifying nuclei solubility and surface energy. While nucleation seems independent from the surfactant, NP's growth depends on it. NP`s size is influenced by the type of functional group (C, O, S or N), length of its C chain and NP to surfactant ratio. In this paper, gold nanoparticles (Au NPs) are taken as model systems to study how nucleation and growth processes are affected by the choice of surfactants by Dissipative Particle Dynamics (DPD) simulations. DPD has been mainly used for studying biochemical structures, like lipid bilayer models. However, the study of solid NPs, and their conjugates, needs the introduction of a new metallic component. To represent the collective phenomena of these large systems, their degrees of freedom are reduced by Coarse-Grained (CG) models. DPD behaved as a powerful tool for studying complex systems and shedding some light on some experimental observations, otherwise difficult to explain.

The Capsid Precursor Protein of Astrovirus VA1 Is Proteolytically Processed Intracellularly.

Human astrovirus VA1 has been associated with neurological disease in immunocompromised patients, and its recent propagation in cell culture has opened the possibility to study its biology. Unlike classical human astroviruses, VA1 growth was found to be independent of trypsin during virus replication in vitro. In this work, we show that despite its independence on trypsin activation for cell infection, the VA1 capsid precursor protein, of 86 kDa (VP86), is processed intracellularly, and this proteolytic processing is important for astrovirus VA1 infectivity. Antibodies raised against different regions of the capsid precursor showed that the polyprotein can be processed starting at either its amino- or carboxy-terminal end, and they allowed us to identify those proteins of about 33 (VP33) and 38 (VP38) kDa constitute the core and the spike proteins of the mature infectious virus particles, respectively. The amino-terminal end of the spike protein was found to be Thr-348. Whether the protease involved in intracellular cleavage of the capsid precursor is of viral or cellular origin remains to be determined, but the cleavage is independent of caspases. Also, trypsin is able to degrade the capsid precursor but has no effect on VP33 and VP38 proteins when assembled into virus particles. These studies provide the basis for advancement of the knowledge of astrovirus VA1 cell entry and replication. IMPORTANCE Human astrovirus VA1 has been associated with neurological disease in immunocompromised patients. Its recent propagation in cell culture has facilitated the study of its biology. In this work, we show that despite the ability of this virus to grow in the absence of trypsin, a marked feature of human classical astroviruses, the capsid precursor protein of astrovirus VA1 is cleaved intracellularly to yield the mature infectious particles, formed by two polypeptides, VP33 that constitutes the core domain of the virus particle, and VP38 that forms the spike of the virus. These studies provide a platform to advance our knowledge on astrovirus VA1 cell entry and replication.

Synthesis and In Vitro Studies of Photoactivatable Semisquaraine-type Pt(II) Complexes.

The synthesis, full characterization, photochemical properties, and cytotoxic activity toward cisplatin-resistant cancer cell lines of new semisquaraine-type Pt(II) complexes are presented. The synthesis of eight semisquaraine-type ligands has been carried out by means of an innovative, straightforward methodology. A thorough structural NMR and X-ray diffraction analysis of the new ligands and complexes has been done. Density functional theory calculations have allowed to assign the trans configuration of the platinum center. Through the structural modification of the ligands, it has been possible to synthesize some complexes, which have turned out to be photoactive at wavelengths that allow their activation in cell cultures and, importantly, two of them show remarkable solubility in biological media. Photodegradation processes have been studied in depth, including the structural identification of photoproducts, thus justifying the changes observed after irradiation. From biological assessment, complexes C7 and C8 have been demonstrated to behave as promising photoactivatable compounds in the assayed cancer cell lines. Upon photoactivation, both complexes are capable of inducing a higher cytotoxic effect on the tested cells compared with nonphotoactivated compounds. Among the observed results, it is remarkable to note that C7 showed a PI > 50 in HeLa cells, and C8 showed a PI > 40 in A2780 cells, being also effective over cisplatin-resistant A2780cis cells (PI = 7 and PI = 4, respectively). The mechanism of action of these complexes has been studied, revealing that these photoactivated platinum complexes would actually present a combined mode of action, a therapeutically potential advantage.

Pooling saliva samples as an excellent option to increase the surveillance for SARS-CoV-2 when re-opening community settings.

In many countries a second wave of infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occurred, triggering a shortage of reagents needed for diagnosis and compromising the capacity of laboratory testing. There is an urgent need to develop methods to accelerate the diagnostic procedures. Pooling samples represents a strategy to overcome the shortage of reagents, since several samples can be tested using one reaction, significantly increasing the number and speed with which tests can be carried out. We have reported the feasibility to use a direct lysis procedure of saliva as source for RNA to SARS-CoV-2 genome detection by reverse transcription quantitative-PCR (RT-qPCR). Here, we show that the direct lysis of saliva pools, of either five or ten samples, does not compromise the detection of viral RNA. In addition, it is a sensitive, fast, and inexpensive method that can be used for massive screening, especially considering the proximity of the reincorporation of activities in universities, offices, and schools.

Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells.

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.

Molecular Detection and Characterization of Porcine Epidemic Diarrhea Virus and Porcine Aichivirus C Coinfection in México.

Swine enteric viral infections are responsible for substantial economic losses in the pork industry worldwide. Porcine epidemic diarrhea (PEDV) is one of the main causative agents of diarrhea in lactating pigs, and reports of PEDV coinfection with other enteric viruses highlight the importance of viral interactions for disease presentation and outcomes. Using next-generation sequencing (NGS) and sequence analyses from samples taken from piglets with acute diarrhea, we explored the possible interactions between PEDV and other less reported pathogens. PEDV coinfection with porcine kobuvirus (PKV) was detected in 36.4% (27/74) of samples. Full genomes from porcine coronavirus and kobuvirus were obtained, as was a partial porcine sapovirus genome (PSaV). The phylogenetic results show the clustering of these strains corresponding to the geographical relationship. To our knowledge, this is the first full genome and isolation report for porcine kobuvirus in México, as well as the first phylogenetic analysis for porcine sapovirus in the country. The NGS approach provides a better perspective of circulating viruses and other pathogens in affected production units.

Influence of High Temperature on the Fracture Properties of Polyolefin Fibre Reinforced Concrete.

Concrete has become the most common construction material, showing, among other advantages, good behaviour when subjected to high temperatures. Nevertheless, concrete is usually reinforced with elements of other materials such as steel in the form of rebars or fibres. Thus, the behaviour under high temperatures of these other materials can be critical for structural elements. In addition, concrete spalling occurs when concrete is subjected to high temperature due to internal pressures. Micro polypropylene fibres (PP) have shown to be effective for reducing such spalling, although this type of fibres barely improves any of the mechanical properties of the element. Hence, a combination of PP with steel rebars or fibres can be effective for the structural design of elements exposed to high temperatures. New polyolefin fibres (PF) have become an alternative to steel fibres. PF meet the requirements of the standards to consider the contributions of the fibres in the structural design. However, there is a lack of evidence about the behaviour of PF and elements made of polyolefin fibre reinforced concrete (PFRC) subjected to high temperatures. Given that these polymer fibres would be melt above 250 °C, the behaviour in the intermediate temperatures was assessed in this study. Uni-axial tests on individual fibres and three-point bending tests of PFRC specimens were performed. The results have shown that the residual load-bearing capacity of the material is gradually lost up to 200 °C, though the PFRC showed structural performance up to 185 °C.

Carbon nanotube transmembrane channel formation and single-stranded DNA spontaneous internalization: a dissipative particle dynamics study.

Single-walled carbon nanotube (SWCNT) transmembrane channel formation in a pure 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) bilayer, and the spontaneous internalization of single-stranded DNA (ssDNA) into the formed pore were simulated. A combination of computational techniques, Dissipative Particle Dynamics-Monte Carlo hybrid simulations and quantum mechanical calculations at the hybrid-DFT level, was used as a new proposal to perform DPD simulations granting specific chemical identity to the model particles. The simulated transmembrane channels showed that, in the case of pristine SWCNTs and upon increasing the nanotube length, a higher tilt angle with respect to the bilayer normal is observed and more time is needed for the nanotube to stabilize. On the other hand, for SWCNTs with polar rims an almost perpendicular orientation is preferred with less than 15° of tilt with respect to the bilayer normal once the nanotubes have pierced both monolayers. These findings are supported by experimental observations where CNTs of average inner diameters of 1.51 ± 0.21 nm and lengths in the 5-15 nm range were inserted in DOPC membranes [J. Geng, et al., Nature, 2014, 514(7524), 612-615]. Moreover, the narrower the SWCNTs, the slower the spontaneous internalization of ssDNA becomes, and ssDNA ends hydrophobically trapped inside the artificial pore. A dependence on the nucleotide content is found indicating that the higher the presence of adenine and thymine in the ssDNA chains the slower the internalization becomes, in agreement with the experimental [A. M. Ababneh, et al., Biophys. J., 2003, 85(2), 1111-1127] and predicted solvation tendency in water for nucleic acid bases.

Saliva Sampling and Its Direct Lysis, an Excellent Option To Increase the Number of SARS-CoV-2 Diagnostic Tests in Settings with Supply Shortages.

As part of any plan to lift or ease the confinement restrictions that are in place in many different countries, there is an urgent need to increase the capacity of laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Detection of the viral genome through reverse transcription-quantitative PCR (RT-qPCR) is the gold standard for this virus; however, the high demand of the materials and reagents needed to sample individuals, purify the viral RNA, and perform the RT-qPCR has resulted in a worldwide shortage of several of these supplies. Here, we show that directly lysed saliva samples can serve as a suitable source for viral RNA detection that is less expensive and can be as efficient as the classical protocol, which involves column purification of the viral RNA. In addition, it bypasses the need for swab sampling, decreases the risk of the health care personnel involved in the testing process, and accelerates the diagnostic procedure.

Astrovirus reverse genetics systems, a story of success.

Astroviruses are one of the main causes of gastroenteritis of medical and veterinary relevance worldwide. Recently, these viruses were associated with neurological disease in mammals, including humans. Reverse genetics systems are the most powerful tool to improve our understanding of the virus replication, and eventually to develop safe vaccine candidates. In the present review, it is summarized the current knowledge on the different strategies used to develop reverse genetics systems for mamastroviruses and avastroviruses, and some of the biological answers that have provided are discussed.

Evidence of Enantiomers of Spiroglycol. Distinction by Using α,α'-Bis(trifluoromethyl)-9,10-anthracenedimethanol as a Chiral Solvating Agent and by Derivatization with Chiral Acids.

Herein, we perform for the first time a preliminary NMR and computational study of the spiroglycol structure. Spiroglycol is a highly symmetrical molecule, but it should be chiral due to the presence of a chiral axis. The presence of two enantiomers was demonstrated performing NMR enantiodifferentiation experiments using α,α'-bis(trifluoromethyl)-9,10-anthracenedimethanol (ABTE) as a chiral solvating agent (CSA). The addition of 0.6 equiv of ABTE allows the differentiation of several spiroglycol proton signals. The lack of resolution observed in the proton spectrum can be tackled through the corresponding 13C NMR spectrum where a significant enantiodifferentiation at the spirocarbon atom was observed. In order to physically separate both enantiomers, a SPG derivatization with camphorsulfonic acid and Mosher's acid was performed affording the corresponding diastereoisomeric ester mixtures. Computations performed with the Gaussian16 package showed that the enantiodifferentiation is mainly due to the different compound thermodynamics stability.

Platinum nanoparticles stabilized by N-heterocyclic thiones. Synthesis and catalytic activity in mono- and di-hydroboration of alkynes.

N-Heterocyclic Thiones (NHT) proved to be efficient ligands for the stabilization of small platinum nanoparticles (1.3-1.7 nm), synthesized by decomposition of [Pt(dba)2], under a H2 atmosphere, in the presence of variable sub-stoichiometric amounts of the NHT. Full characterization by means of TEM, HR-TEM, NMR, ICP, TGA and XPS have been carried out, providing information about the nature of the metal nanoparticles and the interaction of the NHT ligands to the metal surface. Importantly, DFT calculations indicate that some NHT ligands interact with the metal through the C[double bond, length as m-dash]C double bond of the imidazole fragment in addition to the sulfur atom, thus providing additional stabilization to the nanoparticles. According to XPS, TGA and ICP techniques, the surface coverage by the ligand increases by decreasing the size of the substituents on the nitrogen atom. The platinum nanoparticles have been used as catalyst in the hydroboration of alkynes. The most active system is that with a less covered surface area lacking an interaction of the ligand by means of the C[double bond, length as m-dash]C double bond. This catalyst hydroborates alkynes with excellent selectivities towards the monoborylated anti-Markovnikov product (vinyl-boronate) when one equiv. of borane is used. Very interestingly, aliphatic alkynes undergo a second hydroborylation process leading to the corresponding 1,1- and 1,2-diboroylated species with good selectivities towards the former.

Interaction with Modified Cyclodextrin as a Way to Increase the Antimalarial Activity of Primaquine.

BACKGROUND: Malaria is still a dangerous disease that impacts specifically Africa, Asia, and Latin America. The development of therapies to overcome the parasite infection is an important challenge nowadays. The medicine primaquine (PQ) is used in the treatment, although several side effects and low oral bioavailability are reported. OBJECTIVE: This work focused on the preparation and characterization of a complex between PQ and 2- hydroxypropyl-ß-cyclodextrin (HPCD), besides performing release tests of this formulation. METHODS: PQ:HPCD complexes were prepared at 1:1 and 1:2 molar ratios, by the lyophilization method. The association between PQ and HPCD was tested using UV-vis, infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy and NMR techniques (chemical shift, Job Plot, DOSY, and ROESY). Tests were also conducted to evaluate drug release before and after complexation with HPCD. RESULTS: Results showed that there was a weak interaction of PQ with HPCD, forming non-inclusion complexes. These results were supported by FTIR results and spatial correlations between hydrogens from PQ with the external HPCD hydrogens. A 1:2 PQ:HPCD preferred molar ratio was determined by DSC and Job Plot experiments and the time to release 96% of the drug was 21.2 h slower after complexation. CONCLUSION: Conclusion indicate that PQ interacts poorly with HPCD, probably due to its hydrophilic character, as well as to its interaction with the external rim of HPCD. Our results demonstrate that there was a significant improvement in the release time after the complexation process, which could lead to an increase in the activity of the drug.

Development of a novel DNA based reverse genetics system for classic human astroviruses.

Human astroviruses (HAstVs) are a frequent cause of gastroenteritis in young children and immunocompromised patients. The current report describes a new approach to recover genetically defined HAstVs through the use of a reverse genetics system based on a single DNA plasmid. This plasmid, carrying the full-length virus genome under a T7 promoter, is directly transfected into cells expressing T7 RNA polymerase, resulting in the rapid and robust recovery of infectious HAstV. The efficiency of the system was tested with the generation of a chimeric astrovirus having the HAstV serotype 1 replication machinery and the capsid derived from a HAstV serotype 8 virus. This new system provides an efficient and reproducible method to deepen our knowledge of astrovirus biology.

Chitosan as a capping agent: Insights on the stabilization of gold nanoparticles.

A theoretical method based on Dissipative Particle Dynamics (DPD) was applied for the study of the interaction between coarse-grained models of chitosan and gold nanoparticles. These models were used to understand the role of chitosan in the stabilization of gold nanoparticles (5 and 7 nm). In addition, this stabilization was also supported by synthesized and characterized chitosan-gold nanoparticles comparing their stabilities with typical citrate-gold nanoparticles. Finally, the role of chitosan as a capping agent through the steric and electrosteric mechanisms in aqueous media with different pH values was also evaluated.

Phylogenetic Analysis and Characterization of the Complete Hepatitis E Virus Genome (Zoonotic Genotype 3) in Swine Samples from Mexico.

Hepatitis E virus (HEV) is an emerging public health problem with an estimated 20 million infections each year. In Mexico, Orthohepevirus A, genotype 2, has been reported in humans, but genotype 3 has only been reported in swine (zoonotic). No diagnostic tests are publicly available in Mexico, and only partial sequences have been reported from swine samples. Hence, research is necessary to determine circulating strains, understand the features and dynamics of infection on pig farms, determine how to implement surveillance programs, and to assess public health risks. In this study, a next-generation sequencing (NGS) approach was applied to obtain a complete genome of swine HEV. Liver, feces, and bile samples were taken at slaughterhouses and a farm in Mexico. RT-PCR was used to determine positive samples and confirmed by Sanger sequencing. Of the 64 slaughterhouse samples, one bile sample was positive (B1r) (1.56%). Of 21 sample pools from farm animals, 14 were positive (66.66%), representing all stages of production. A complete sequence strain MXCDg3_B1c|_2016 was obtained from the bile of a domestic swine in the fattening stage. In addition, two partial sequences-MXCDg3_H2cons|_2016 (1473 nt) and MXCDg3_C3Acons|_2016 (4777 nt)-were obtained from sampled farm animals. Comparison with all reported genome HEV sequences showed similarity to genotype 3 subgenotype a (G3a), which has been previously reported in acute cases of human hepatitis in the US, Colombia, China, and Japan.

Complexes between methyltestosterone and ß-cyclodextrin for application in aquaculture production.

The inclusion complexes between 17-α-methyltestosterone (MT) and ß-cyclodextrin (bCD) were prepared and characterized in dissolution and solid phase. The complex promoted a sixfold increment in solubility of the hormone. It has a limited solubility and stoichiometry of 2:1 (bCD:MT) determined by DSC, NMR and solubility experiments, the association constant Ka=2846Lmol-1 and complex fraction of 76% (assessed by DOSY-NMR, in (1:3) DMSO/D2O). The association constant obtained in water by the solubility isotherms is 7540Lmol-1. 2D-ROESY experiments indicate the intermolecular orientation (complete inclusion of the hormone in the cavity). Simulations by molecular dynamics agreed with the formation of the inclusion complex 2:1. Release tests showed the slower release for the complexes, with 50% for lyophilization and 56% for malaxation. These results clearly demonstrate the complexation of MT in bCD, which formulations are promising for further applications involving this steroid in aquaculture, both for sexual reversal and in technologies of hormone in water sequestration.

Domain Formation and Conformational Changes in Gold Nanoparticle Conjugates Studied Using DPD Simulations.

A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA) and thiolated polyethylene glycol (SH-PEG) is simulated using dissipative particle dynamics (DPD) methods, obtaining an excellent agreement with previous experimental observations. The simulations cover the isolated components (AuNP, MUA, and SH-PEG), as well as pairs of components, and finally the all three components at the same time. In this latter case, changes in the order of addition of MUA and SH-PEG over the AuNP are also considered. The AuNP is formed by independent gold beads and keeps an almost spherical shape throughout the simulation. MUA forms micelles of four to six MUA units when dispersed in water, while SH-PEG stays individually and well solvated. When exposed to AuNP, both molecules show a tendency to form patches on the surface. SH-PEG displays two different conformations (radial and tangential) depending on its relative concentration and the presence of other molecules at the NP surface. When combined at subsaturation concentrations, MUA arrives faster to the AuNP surface than SH-PEG and forms patches while SH-PEG occupies the remaining free surface. In these conditions, the order of addition of the different components partially alters these results. When SH-PEG is added over an already formed MUA/AuNP partial layer, it adopts a radial conformation over the MUA formed patches; on the contrary, if MUA is added over an already formed SH-PEG/AuNP partial layer, much less SH-PEGs adopt a radial conformation and MUA patches are significantly smaller.

Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells.

The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.IMPORTANCE Vesiviruses, such as San Miguel sea lion virus and feline calicivirus, are typically associated with infection in animal hosts. Following the accidental infection of a laboratory worker with San Miguel sea lion virus, a related virus was isolated in cell culture and named Hom-1. In this study, we found that Hom-1 could be propagated in a number of human cell lines, making it the first calicivirus to replicate efficiently in cultured human cells. Screening of a library of human cell surface membrane proteins showed that the virus could utilize human junctional adhesion molecule 1 as a receptor to enter cells and initiate replication. The Hom-1 virus presents a new system for the study of calicivirus biology and species specificity.