Advancement in the development of gene/protein-based vaccines against African swine fever virus.

African swine fever (ASF) is a highly contagious acute hemorrhagic viral disease, with the mortality rate of up to 100 % in domestic pigs. In recent years, ASF outbreaks have caused huge economic losses in numerous countries and regions, especially in Asia. Therefore, there is a pressing need to develop safe and effective vaccines against infection of the causative pathogen, African swine fever virus (ASFV).

Nonenveloped Avian Reoviruses Released with Small Extracellular Vesicles Are Highly Infectious.

Vesicle-encapsulated nonenveloped viruses are a recently recognized alternate form of nonenveloped viruses that can avoid immune detection and potentially increase systemic transmission. Avian orthoreoviruses (ARVs) are the leading cause of various disease conditions among birds and poultry. However, whether ARVs use cellular vesicle trafficking routes for egress and cell-to-cell transmission is still poorly understood.

Potential cross-species transmission of highly pathogenic avian influenza H5 subtype (HPAI H5) viruses to humans calls for the development of H5-specific and universal influenza vaccines.

In recent years, highly pathogenic avian influenza H5 subtype (HPAI H5) viruses have been prevalent around the world in both avian and mammalian species, causing serious economic losses to farmers. HPAI H5 infections of zoonotic origin also pose a threat to human health. Upon evaluating the global distribution of HPAI H5 viruses from 2019 to 2022, we found that the dominant strain of HPAI H5 rapidly changed from H5N8 to H5N1.

Natural variant R246K in hemagglutinin increased zoonotic characteristics and renal inflammation in mice infected with H9N2 influenza virus.

Considered a potential pandemic candidate, the widespread among poultry of H9N2 avian influenza viruses across Asia and North Africa pose an increasing threat to poultry and human health. The massive epidemic of H9N2 viruses has expanded the host range; however, the molecular basis and characteristic underlying the transmission to poultry and mammals remains unclear. Our previous study has proved that some natural mutations in the HA gene enhanced the binding ability of the H9N2 virus to α-2,6 SA receptors.

A quadruple protection procedure for resuming pig production in small-scale ASFV-positive farms in China.

African swine fever (ASF) outbreak has caused serious economic losses in Asia since 2018. As ASF is a new emerging disease, many farmers hesitate to raise pigs before biosafety procedures were evaluated to be effective. To support small-scale farms in resuming pig production, a comprehensive procedure, called the quadruple protection procedure (QPP), was tested in 35 small farms which had been confirmed with African swine fever virus (ASFV).

COVID-19 Pandemic: The Influence of Culture and Lessons for Collaborative Activities.

The rapid epidemiological shift from an epidemic/outbreak in Wuhan, China, to a global pandemic of COVID-19 in less than 3 months came with lessons the world's health system should learn to prepare for the future outbreaks. Since February 20, 2020, the total number of confirmed cases of COVID-19 has been increased very slowly in the countries of East Asia, including Japan, South Korea, and China, when compared with those in the Western countries. This chapter begins with an overview of the impact of COVID-19 on healthcare workers and public health facilities, followed by immediate global actions and research in response to the newly emerged pandemic.

Rapid detection of SARS-CoV-2, replicating or non-replicating, using RT-PCR.

To identify animals susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or to determine whether SARS-CoV-2 contaminated meat is from a SARS-CoV-2-infected animal, a convenient and safe method was developed for rapid detection of SARS-CoV-2 in a replicating or non-replicating status in samples using reverse transcriptase-polymerase chain reaction (RT-PCR). This strategy can also be applied to develop assays for the detection of other viruses, either replicating or not.

Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs).

Lessons learned from the 2019-nCoV epidemic on prevention of future infectious diseases.

Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated-Hubei province, whose capital city is Wuhan.

Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China.

On 10 January 2020, a new coronavirus causing a pneumonia outbreak in Wuhan City in central China was denoted as 2019-nCoV by the World Health Organization (WHO). As of 24 January 2020, there were 887 confirmed cases of 2019-nCoV infection, including 26 deaths, reported in China and other countries. Therefore, combating this new virus and stopping the epidemic is a matter of urgency.

Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models.

The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral fusogens (∼100-150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy.

Peptides derived from HIV-1 gp120 co-receptor binding domain form amyloid fibrils and enhance HIV-1 infection.

Amyloid fibrils play important roles in HIV-1 infection. We found peptides derived from the HIV-1 gp120 co-receptor binding region, which are defined as enhancing peptides (EPs), could form amyloid fibrils and remarkably enhance HIV-1 infection. EPs bound to the virus and promoted the interaction between HIV-1 and target cells.

F(ab')2 fragment of a gp41 NHR-trimer-induced IgM monoclonal antibody neutralizes HIV-1 infection and blocks viral fusion by targeting the conserved gp41 pocket.

Using a recombinant protein N46FdFc that mimics the HIV-1 gp41 N-helix trimer to immunize mice, we identified the first IgM monoclonal antibody 18D3 that specifically bound to the conserved gp41 pocket. Its F(ab')2 fragment potently inhibited HIV-1 Env-mediated cell-cell fusion and neutralized infection by laboratory-adapted and primary HIV-1 isolates with different subtypes and tropism, including the T20-resistant variants. This F(ab')2 fragment can be used to develop a bispecific broad neutralizing monoclonal antibody or HIV-1 inactivator as a novel immunotherapeutic for treatment and prevention of HIV-1 infection.

A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains.

Background: Most currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors) must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells.

The conserved residue Arg46 in the N-terminal heptad repeat domain of HIV-1 gp41 is critical for viral fusion and entry.

During the process of HIV-1 fusion with the target cell, the N-terminal heptad repeat (NHR) of gp41 interacts with the C-terminal heptad repeat (CHR) to form fusogenic six-helix bundle (6-HB) core. We previously identified a crucial residue for 6-HB formation and virus entry--Lys63 (K63) in the C-terminal region of NHR (aa 54-70), which forms a hydrophobic cavity. It can form an important salt bridge with Asp121 (D121) in gp41 CHR.

HIV-1 variants with a single-point mutation in the gp41 pocket region exhibiting different susceptibility to HIV fusion inhibitors with pocket- or membrane-binding domain.

Enfuvirtide (T20), the first FDA-approved peptide HIV fusion/entry inhibitor derived from the HIV-1 gp41 C-terminal heptad-repeat (CHR) domain, is believed to share a target with C34, another well-characterized CHR-peptide, by interacting with the gp41 N-terminal heptad-repeat (NHR) to form six-helix bundle core. However, our previous studies showed that T20 mainly interacts with the N-terminal region of the NHR (N-NHR) and lipid membranes, while C34 mainly binds to the NHR C-terminal pocket region. But so far, no one has shown that C34 can induce drug-resistance mutation in the gp41 pocket region.

Phylogenetic and biological analysis of a laboratory-generated gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV).

A xenotropic murine leukemia virus-related virus (XMRV) has been reported to be an emerging pathogen associated with prostate cancer (PC) and chronic fatigue syndrome (CFS). However, recent studies have demonstrated that XMRV is a laboratory-derived virus resulting from genetic recombination between two mouse viral genomes during serial xenograft tissue transplantation. This study describes a phylogenetic analysis that compared XMRV with the ecotropic murine leukemia viruses (E-MLV), xenotropic MLV (X-MLV), and other retroviruses, including HTLV-1 and HIV-1.

Interactions between different generation HIV-1 fusion inhibitors and the putative mechanism underlying the synergistic anti-HIV-1 effect resulting from their combination.

We previously reported that the combinatorial use of T20 and T1144, the first and next generations of HIV fusion inhibitors, containing different functional domains resulted in synergistic anti-HIV-1 effect, but this effect diminished when T20 and T1144 were covalently linked together. To elucidate the mechanism underlying this synergistic anti-HIV-1 effect, we studied the interactions between T20 and T1144 either in a mixture state or in a covalently linked state. T20 alone in solution was largely featureless, while T1144 alone was in α-helical trimeric conformation.

A novel chimeric protein-based HIV-1 fusion inhibitor targeting gp41 glycoprotein with high potency and stability.

T20 (enfuvirtide, Fuzeon) is the first generation HIV-1 fusion inhibitor approved for salvage therapy of HIV-1-infected patients refractory to current antiretroviral drugs. However, its application is limited by the high cost of peptide synthesis, rapid proteolysis, and poor efficacy against emerging drug-resistant strains. Here we reported the design of a novel chimera protein-based fusion inhibitor targeting gp41, TLT35, that uses a flexible 35-mer linker to couple T20 and T1144, the first and next generation HIV-1 fusion inhibitors, respectively.

CL-385319 inhibits H5N1 avian influenza A virus infection by blocking viral entry.

CL-385319, an N-substituted piperidine, is effective in inhibiting infection of H1-, H2-, and to a lesser extent, H3-typed influenza A viruses by interfering with the fusogenic function of the viral hemagglutinin. Here we show that CL-385319 is effective in inhibiting infection of highly pathogenic H5N1 influenza A virus in Madin-Darby Canine Kidney (MDCK) cells with an IC50 of 27.03±2.

Fab crystallization and preliminary X-ray analysis of NC-1, an anti-HIV-1 antibody that recognizes the six-helix bundle core of gp41.

NC-1 is a murine monoclonal antibody that specifically recognizes the six-helix bundle core of the human immunodeficiency virus type 1 (HIV-1) gp41. As such, it is a useful tool for probing gp41 conformations in HIV-1 membrane fusion. To establish the structural basis underlying the NC-1 specificity, X-ray crystallography was employed to solve its three-dimensional structure.