The entry process of viruses into host cells is complex and involves stable but transient multivalent interactions with different cell surface receptors. The initial contact of several viruses begins with attachment to heparan sulfate (HS) proteoglycans on the cell surface, which results in a cascade of events that end up with virus entry. The development of antiviral agents based on multivalent interactions to shield virus particles and block initial interactions with cellular receptors has attracted attention in antiviral research. Here, we designed nanogels with different degrees of flexibility based on dendritic polyglycerol sulfate to mimic cellular HS. The designed nanogels are nontoxic and broad-spectrum, can multivalently interact with viral glycoproteins, shield virus surfaces, and efficiently block infection. We also visualized virus-nanogel interactions as well as the uptake of nanogels by the cells through clathrin-mediated endocytosis using confocal microscopy. As many human viruses attach to the cells through HS moieties, we introduce our flexible nanogels as robust inhibitors for these viruses.
Since 2006, more and more cases of the infectious H3N2 canine influenza virus (CIV) in pet dogs have been reported in southern China. However, little is known about the prevalence situation of H3N2 CIV infections in farmed dogs in China. This is the first systematic epidemiological surveillance of CIV in different dog populations in southern China. Two virus strains A/Canine/Guangdong/1/2011(H3N2) and A/canine/Guangdong/5/2011(H3N2) were isolated from canine nasal swabs collected at one dog farm in Guangzhou and the other farm in Shenzhen. Sequence and phylogenetic analysis of eight gene segments of these viruses revealed that they were most similar to the newly isolated canine H3N2 viruses in dogs and cats from Korea and China, which originated from avian strain. This indicates that H3N2 CIV may be a common pathogen for pet and farmed dog populations in southern China at present. Serological surveillance has shown that the infection rate of this avian-origin canine influenza in farmed dogs and in pet dogs were 12.22% and 5.3%, respectively; as determined by the ELISA. The data also suggested that transmission occurred, most probably by close contact, between H3N2 CIV infected dogs in different dog populations in recently years. As H3N2 outbreaks among dogs continue in the Guangdong province (located very close to Hong Kong), the areas where is densely populated and with frequent animal trade, there is a continued risk for pets H3N2 CIV infections and for mutations or genetic reassortment leading to new virus strains with increased transmissibility among dogs. Further in-depth study is required as the H3N2 CIV has been established in different dog populations and posed potential threat to public health.
Nonstructural protein 7 (nsp7), which is flanked by nsp6 and nsp8, is one of the most conserved nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV). Nonstructural protein (nsp)-specific antibodies are produced in high titers in response to virus replication, especially against nsp1a, nsp1b, nsp2, and nsp7. However, many regional aspects of nsp7 are still veiled, such as its impact on viral replication and virulence or the immunological mechanism between virus and host. Based on the structure of the predicted nsp7 domain, we have constructed a series of large mutations and deletions. We ultimately demonstrated all mutations (nsp7, nsp7α/nspβ) and the majority of substitutions of nsp7 affected the PRRSV replicative cycle in some ways and were fatal for viral recovery, which indicates that these are significant to structure or function of the nsp7. What's more, the mutant vOKXH-nsp7 (F40A) indeed caused some of the variation compared with the parental virus vOKXH-GD, which shortens the amount of time needed to reach its highest viral titer, and decreases the concentration of the highest viral titer, obstructing viral mRNA and protein synthesis. Consequently, these valuable results possibly provide the first direct evidence that the nsp7 is really a critical protein domain for the RNA synthesis and the translation of viral protein of PRRSV.
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