The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection.

Enterovirus A71 2A-S125A acts as an attenuated vaccine candidate, indicating a universal approach in developing enterovirus vaccines.

Enteroviruses are important human pathogens with diverse serotypes, posing a major challenge to develop vaccines for individual serotypes, the success of polio vaccines in controlling and eradicating polio, along with the recent emergence and high prevalence of enterovirus-caused infectious diseases, highlights the importance of enterovirus vaccine development. Given our previous report on enteroviruses weakened by the 2 A S/T125A mutation, we assessed the potential of the EV-A71 2A-125A mutant as a vaccine candidate to address this challenge. We found that the 2A-125A mutant caused transient mild symptoms, low viral loads, and no significant pathological changes mild pathological changes in hSCARB2-KI mice, producing long-lasting cross-neutralizing antibodies against two EV-A71 wild strains.

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies.

Development of a Bioluminescent Imaging Mouse Model for SARS-CoV-2 Infection Based on a Pseudovirus System.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains widely pandemic around the world. Animal models that are sensitive to the virus are therefore urgently needed to evaluate potential vaccines and antiviral agents; however, SARS-CoV-2 requires biosafety level 3 containment. To overcome this, we developed an animal model using the intranasal administration of SARS-CoV-2 pseudovirus.

Phosphorylation of enteroviral 2A at Ser/Thr125 benefits its proteolytic activity and viral pathogenesis.

Enteroviral 2A proteinase (2A ), a well-established and important viral functional protein, plays a key role in shutting down cellular cap-dependent translation, mainly via its proteolytic activity, and creating optimal conditions for Enterovirus survival. Accumulated data show that viruses take advantage of various signaling cascades for their life cycle; studies performed by us and others have demonstrated that the extracellular signal-regulated kinase (ERK) pathway is essential for enterovirus A71 (EV-A71) and other viruses replication. We recently showed that ERK1/2 is required for the proteolytic activity of viral 2A ; however, the mechanism underlying the regulation of 2A remains unknown.

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein.

Novel hKDR mouse model depicts the antiangiogenesis and apoptosis-promoting effects of neutralizing antibodies targeting vascular endothelial growth factor receptor 2.

Vascular endothelial growth factor receptor 2 (VEGFR2)/KDR plays a critical role in tumor growth, diffusion, and invasion. The amino acid sequence homology of KDR between mouse and human in the VEGF ligand-binding domain was low, thus the WT mice could not be used to evaluate Abs against human KDR, and the lack of a suitable mouse model hindered both basic research and drug developments. Using the CRISPR/Cas9 technique, we successfully inserted different fragments of the human KDR coding sequence into the chromosomal mouse Kdr exon 4 locus to obtain an hKDR humanized mouse that can be used to evaluate the marketed Ab ramucirumab.

Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus.

Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a gene knockout using CRISPR/Cas9 technology.

Animal models for COVID-19: advances, gaps and perspectives.

COVID-19, caused by SARS-CoV-2, is the most consequential pandemic of this century. Since the outbreak in late 2019, animal models have been playing crucial roles in aiding the rapid development of vaccines/drugs for prevention and therapy, as well as understanding the pathogenesis of SARS-CoV-2 infection and immune responses of hosts. However, the current animal models have some deficits and there is an urgent need for novel models to evaluate the virulence of variants of concerns (VOC), antibody-dependent enhancement (ADE), and various comorbidities of COVID-19.

Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection.

Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.

Generation of a uniform thymic malignant lymphoma model with C57BL/6J gene deficient mice.

Lymphoma is the third most common cancer diagnosed in children, and T-cell lymphoma has the worst prognosis based on clinical observations. To date, a lymphoma model with uniform penetrance has not yet been developed. In this study, we generated a deficient mouse model by targeting embryonic stem cells derived from a C57BL/6J mouse strain.

Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2.

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations.

A practical method for evaluating the efficacy of EVA-71 vaccine using a hSCARB2 knock-in mouse model.

Hand-foot-and-mouth disease is a contagious disease common among children under 5 years old worldwide. It is caused by strains of enterovirus, especially EV-A71, which can lead to severe disease. Vaccines are the only way to fight this disease.

A new nairo-like virus associated with human febrile illness in China.

Several nairo-like viruses have been discovered in ticks in recent years, but their relevance to public health remains unknown. Here, we found a patient who had a history of tick bite and suffered from a febrile illness was infected with a previously discovered RNA virus, Beiji nairovirus (BJNV), in the nairo-like virus group of the order . We isolated the virus by cell culture assay.

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development.

To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity.

Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay.

Pseudotyped viruses are useful virological tools because of their safety and versatility. On the basis of a vesicular stomatitis virus (VSV) pseudotyped virus production system, we developed a pseudotyped virus-based neutralization assay against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in biosafety level 2 facilities. Compared with the binding antibody test, the neutralization assay could discriminate the protective agents from the antibody family.

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells.

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD).