Virology Journal

The HIV surface glycoprotein gp120 (SU, gp120) and the Plasmodium vivax Duffy binding protein (PvDBP) bind to chemokine receptors during infection and have a site of amino acid sequence similarity in their binding domains that often includes a heparin binding motif (HBM). Infection by either pathogen has been found to be inhibited by polyanions. Specific polyanions that inhibit HIV infection and bind to the V3 loop of X4 strains also inhibited DBP-mediated infection of erythrocytes and DBP binding to the Duffy Antigen Receptor for Chemokines (DARC). A peptide including the HBM of PvDBP had similar affinity for heparin as RANTES and V3 loop peptides, and could be specifically inhibited from heparin binding by the same polyanions that inhibit DBP binding to DARC. However, some V3 peptides can competitively inhibit RANTES binding to heparin, but not the PvDBP HBM peptide. Three other members of the DBP family have an HBM sequence that is necessary for erythrocyte binding, however only the protein which binds to DARC, the P. knowlesi alpha protein, is inhibited by heparin from binding to erythrocytes. Heparitinase digestion does not affect the binding of DBP to erythrocytes. The HBMs of DBPs that bind to DARC have similar heparin binding affinities as some V3 loop peptides and chemokines, are responsible for specific sulfated polysaccharide inhibition of parasite binding and invasion of red blood cells, and are more likely to bind to negative charges on the receptor than cell surface glycosaminoglycans.

Swine influenza viruses (SIV), considered the “mixing vessels” of influenza viruses, posed a significant threat to global health systems and are dangerous pathogens. Eurasian avian-like H1N1(EA-H1N1) viruses have become predominant in swine populations in China since 2016. Lung tissue samples were obtained from pregnant sows with miscarriage and respiratory disease in Heilongjiang province, and pathogens were detected by Next-generation sequencing (NGS) and PCR. The nucleic acid of isolates was extracted to detect SIV by RT-PCR. Then, SIV-positive samples were inoculated into embryonated chicken eggs. After successive generations, the isolates were identified by RT-PCR, IFA, WB and TEM. The genetic evolution and pathogenicity to mice of A/swine/Heilongjiang/GN/2020 were analyzed. The major pathogens were influenza virus (31%), Simbu orthobunyavirus (15%) and Jingmen tick virus (8%) by NGS, while the pathogen that can cause miscarriage and respiratory disease was influenza virus. The SIV(A/swine/Heilongjiang/GN/2020) with hemagglutination activity was isolated from lung samples and was successfully identified by RT-PCR, IFA, WB and TEM. Homology and phylogenetic analysis showed that A/swine/Heilongjiang/GN/2020 is most closely related to A/swine/Henan/SN/10/2018 and belonged to EA-H1N1. Pathogenicity in mice showed that the EA-H1N1 could cause lethal or exhibit extrapulmonary virus spread and cause severe damage to respiratory tracts effectively proliferating in lung and trachea. A/swine/Heilongjiang/GN/2020 (EA-H1N1) virus was isolated from pregnant sows with miscarriage and respiratory disease in Heilongjiang province, China. Clinical signs associated with influenza infection were observed during 14 days with A/swine/Heilongjiang/GN/2020 infected mice. These data suggest that A/swine/Heilongjiang/GN/2020 (EA-H1N1) had high pathogenicity and could be systemic spread in mice.

This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis. Participants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log10 transformed cytokines and ALT values were used in the analysis. Among 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1β) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1β: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1β: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (β = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1β levels. During acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1β levels. These data suggest that IP-10 and MIP-1β may have a role in HCV immuno-pathogenesis starting early in acute HCV infection.

Phylogenetic studies indicate bats as original hosts of SARS-CoV-2. However, it remains unclear whether other animals, including pets, are crucial in the spread and maintenance of COVID-19 worldwide. In this study, we analyzed the first fatal case of a SARS-CoV-2 and FeLV co-infection in an eight-year-old male cat. We carried out a clinical evaluation and several laboratory analyses. As main results, we observed an animal presenting severe acute respiratory syndrome and lesions in several organs, which led to the animal’s death. RT-qPCR analysis showed a SARS-CoV-2 as the causative agent. The virus was detected in several organs, indicating a multisystemic infection. The virus was found in a high load in the trachea, suggesting that the animal may have contribute to the transmission of the virus. The whole-genome sequencing revealed an infection by SARS-CoV-2 Gamma VOC (P.1), and any mutations indicating host adaptation were observed. Our data show that FeLV-positive cats are susceptible to SARS-CoV-2 infection and raise questions about the potential of immunocompromised FeLV-positive cats to act as a reservoir for SARS-CoV-2 new variants.

Herpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501, At present, there are many studies on the anti-tumor, anti-clotting, anti-oxidant and immunoinflammatory effects of Aspergillipeptide D, but little research has been done on the anti-HSV-1 activity of Aspergillipeptide D. The anti-HSV-1 activity of Aspergillipeptide D was evaluated by plaque reduction assay. The mechanism of action against HSV-1 was determined from the effective stage. Then we assayed the viral DNA replication, viral RNA synthesis and protein expression, respectively. We also identified the proteins that interact with gB by mass spectrometry, and assayed the effect of Aspergillipeptide D on the interaction between the virus gB protein and cell proteins. Plaque reduction experiments showed that Aspergillipeptide D did not affect HSV-1 early infection events, including viral inactivation, attachment and penetration. Interestingly, Aspergillipeptide D dramatically reduced both the gene and protein levels of viral late protein gB, and suppressed its location in the endoplasmic reticulum and Golgi apparatus. In contrast, overexpression of gB restored viral production. Finally, proteomic analysis revealed that the numbers of cellular proteins that interacted with gB protein was largely decreased by Aspergillipeptide D. These results suggested that Aspergillipeptide D inhibited gB function to affect HSV-1 intercellular spread. Our results indicated that Aspergillipeptide D might be a potential candidate for HSV-1 therapy, especially for ACV-resistant strains.

The pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery. However, their ability in inhibiting viral infections has not yet been tested. The antiviral activity of the pimprinine family of compounds was evaluated by determining the cytopathic effect (CPE), cell viability or plaque-forming unit (PFU), and virus yield. The mechanism of action against EV71 was determined from the virucidal activity, and effective stage and time-of-addition assays. The effects on EV71 replication were evaluated further by determining viral RNA synthesis, protein expression and cells apoptosis using the SYBR Green assays, immunofluorescence assays and flow cytometric assays, respectively. Pimprinethine, WS-30581 A and WS-30581 B inhibited EV71-induced CPE, reduced progeny EV71 yields, as well as prevented EV71-induced apoptosis in human rhabdomyosarcoma (RD) cells. These compounds were found to target the early stages of the EV71 replication in cells including viral RNA replication and protein synthesis. They also showed antiviral activity against ADV-7, and were slightly active against CVB3, HSV-1 and H1N1 with a few exceptions. Pimprinine was slightly active or inactive against all the viruses tested. The mechanisms by which these compounds act against the viruses tested may be similar to that demonstrated for EV71. The data described herein demonstrate that the pimprinine family of compounds are inhibitors effective against the replication of EV71 and ADV-7, so they might be feasible therapeutic agents for the treatment of viral infections.

Musk deer can produce musk which has high medicinal value and is closely related to human health. Viruses in forest musk deer both threaten the health of forest musk deer and human beings. Using viral metagenomics we investigated the virome in 85 faeces samples collected from forest musk deer. In this article, eight novel CRESS-DNA viruses were characterized, whole genomes were 2148 nt–3852 nt in length. Phylogenetic analysis indicated that some viral genomes were part of four different groups of CRESS-DNA virus belonging in the unclassified CRESS-DNA virus, Smacoviridae, pCPa-like virus and pPAPh2-like virus. UJSL001 (MN621482), UJSL003 (MN621469) and UJSL017 (MN621476) fall into the branch of unclassified CRESS-DNA virus (CRESSV1–2), UJSL002 (MN621468), UJSL004 (MN621481) and UJSL007 (MN621470) belong to the cluster of Smacoviridae, UJSL005 (MN604398) showing close relationship with pCPa-like (pCRESS4–8) clusters and UJSL006 (MN621480) clustered into the branch of pPAPh2-like (pCRESS9) virus, respectively. The virome in faeces samples of forest musk deer from Chengdu, Sichuan province, China was revealed, which further characterized the diversity of viruses in forest musk deer intestinal tract.