instruction:
In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
question:
Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. However, resistant strains may impose substantial challenges. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs). Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and β23/loop V5/β24 of HIV-1 gp120. The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface. Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies. Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes. Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. Among the bnAbs isolated to date, those targeting the CD4bs are the most abundant and thoroughly studied as they disrupt the crucial step of viral interaction with the cellular receptor molecule CD4. Despite the superior potency and breadth of these CD4bs bnAbs, each fails to neutralize a small but significant portion of pseudotyped virus panels. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4bs. Resistance is largely attributed to mutated residues within the epitopes or steric hindrance imposed by the bulky side-chain or glycan shield of the mutated residues, and is largely correlated with reduced binding avidity of the antibody to the quaternary trimeric envelope protein expressed on the PLOS Pathogens | https://doi.surface of the transfected cells. Treatment strategies based on the CD4bs bnAbs therefore must overcome such resistance to achieve optimal clinical outcomes. Recent scientific advances have identified a growing number of broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus type I (HIV-1), providing promising candidates for HIV-1 prevention and treatment [1] [2] [3] [4] [5] . Compared with bnAbs isolated in earlier studies, these bnAbs demonstrated broader and more potent activity against global HIV-1 panels and displayed impressive safety and efficacy profiles for therapeutic applications in a number of animal models and human clinical trials [1, [6] [7] [8] [9] [10] [11] . These results also offer the opportunity to tailor these antibodies and maximize their prevention and treatment potential. Broadly speaking, these bnAbs recognize six major "vulnerable sites" on the HIV-1 envelope glycoprotein gp160 (gp120 and gp41), which are (1) the CD4-binding site (CD4bs), (2) the V1V2 apex, (3) the V3 glycan, (4) the fusion peptide (FP), (5) subunit interface and (6) membrane proximal external region (MPER) of gp41[1-5]. These bnAbs neutralize HIV-1 by blocking viral entry into the target cells, although additional effector functions are likely at play, particularly in the context of in vivo infection and clinical application[1, 12-16]. Among the bnAbs isolated to date, those targeting the CD4bs are the most abundant and thoroughly studied as they disrupt the first and crucial step of viral interaction with the cellular receptor CD4 [3, 4, 17, 18] . In this step, the trimeric envelope glycoprotein, composed of gp120 and gp41, binds with the target cell through the receptor CD4, with either CCR5 or CXCR4 as co-receptor [19] [20] [21] . This triggers a cascade of conformational changes that fuses the viral envelope with the target membrane and releases the viral genome into the cell [22, 23] .More than two dozen CD4bs bnAbs have been isolated to date. This number is likely to grow with the advent of more specific and high-throughput techniques for isolating antibodies.For instance, the prototype VRC01 and its close relative VRC03, which effectively neutralize a panel of diverse pseudotyped viruses,were isolated from a clade-B infected individual [24] [25] [26] . The more recently isolated CD4bs bnAbs, such as 3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31, 12A12, CH103, 8ANC131, VRC13, and VRC16, have shown similar or even enhanced potency and breadth compared with VRC01 [1-5, 27, 28].The CD4bs bnAbs are classified into two groups based on their mode of recognition and heavy chain characteristics, such as the VRC01 class(3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31 and 12A12) and non-VRC01 classes (CH103, 8ANC131, VRC13 and VRC16) [17, 18] . Structurally, these bnAbs recognize residues within the inner domain, the Loop D, the CD4 binding loop, and the β23/loop V5/β24 region [17, 18, [29] [30] [31] .The V1V2 and V3 loop also impact recognition,particularly in the context of the quaternary trimeric envelope protein [32] [33] [34] [35] [36] .The primary mechanism of neutralization mimics and competes with the CD4 receptorto bind HIV-1 gp120, thereby preventing bound trimers from transitioning to the subsequent steps required for membrane fusion, although evidence indicates that there are differences in the fine details of this process [17, 18, 35, 36] . Despite the superior potency and breadth of these CD4bs bnAbs, each fails to neutralize a small but significant portion of pseudotyped virus panels [17, 25, 27, 28, 37, 38].For instance, VRC01 is unable to neutralize about 10% of tested viruses [25] , and resistant strains have been isolated from patients infected with subtype B, subtype C, CRF07_BC, and CRF08_BC[29, [39] [40] [41] [42] . Furthermore, reports show thatVRC01-, 3BNC117-and N6-resistant strains have emerged in both animal models and human clinical trials [11, 15, [43] [44] [45] [46] [47] , indicating that resistant virus Broadly resistant HIV-1 against CD4bs antibodies PLOS Pathogens | https://doi.org/10.
answer:
Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies


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strains of infectious bronchitis virus (IBV) were isolated from the vaccinated chicken flocks in Sichuan province, China. The S1 genes of the isolates were amplified and sequenced. Phylogenetic analysis revealed that the 19 isolates and 37 reference IBV strains can be grouped into eight genotypes. Although IBVs of Taiwan-I type, massachusetts type, and proventriculitis type were isolated, but most isolates were LX4 genotype. Homology analysis of the sequences of S1 genes of the 19 isolates and 37 reference IBV strains revealed that the identity of the nucleotides and amino acid sequences of the S1 genes between the 15 LX4-type isolates and other IBV strains were 71.9-99.3% and 72.1-99.1%, respectively, while those of the analyzed IBV of LX4 type were 96.0-99.9% and 94.3-99.8%, respectively. The results from this study and other published results in the GenBank database showed that isolates circulating in Sichuan province in recent years were mainly LX4 genotype, which is the predominant genotype circulated in China in recent years.
answer:
Genetic analysis revealed LX4 genotype strains of avian infectious bronchitis virus became predominant in recent years in Sichuan area, China


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The unclassified bovine enteric calicivirus (BEC) is a new bovine enteric calicivirus that is different from bovine norovirus, and causes diarrhea and pathologies in the small intestine of calves. This virus includes Nebraska (NB)-and Newbury agent 1 (NA1)-like strains. The prevalence of this BEC and its genetic characterization has only been reported in the UK and the USA. This study examined the prevalence and genetic diversity of these BECs in diarrheic calves in South Korea. Among a total of 645 diarrheic fecal specimens obtained from 629 cattle herds, these unclassified BECs were detected in 59 (9.1%) diarrheic fecal samples from 57 herds (9.3%) by either RT-PCR or nested PCR. Sequence and phylogenetic analyses of the partial RdRp gene showed that all the Korean BECs clustered together and were closely related to the NB-like viruses (80.9-88.1% nucleotide and 84.5-98.4% amino acid) but not to the NA1-like viruses (75.8-78.4% nucleotide and 79.7-82.8% amino acid). Although these viruses could not be classified into NA1-and NB-like viruses from the sequence and phylogenetic data of the entire capsid gene, all the Korean BECs clustered together on a branch separate from the other known BECs. These results show that these BEC infections are endemic in diarrheic calves in South Korea. The infecting strains are genetically closer to the NB-like viruses but have a distinct evolutionary pathway. #
answer:

Molecular detection and characterization of unclassified bovine enteric caliciviruses in South Korea