• Title/Summary/Keyword: virus entry

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Characterization of Prototype Foamy Virus Infectivity in Transportin 3 Knockdown Human 293t Cell Line

  • Hamid, Faysal Bin;Kim, Jinsun;Shin, Cha-Gyun
    • Journal of Microbiology and Biotechnology
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    • v.27 no.2
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    • pp.380-387
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    • 2017
  • The foamy viruses are currently considered essential for development as vectors for gene delivery. Previous studies demonstrated that prototype foamy virus (PFV) can infect and replicate prevalently in a variety of cell types for its exclusive replication strategy. However, the virus-host interaction, especially PFV-transportin3 (TNPO3), is still poorly understood. In our investigation of the role of TNPO3 in PFV infection, we found lower virus production in TNPO3 knockdown (KD) cells compared with wild-type 293T cells. PCR analysis revealed that viral DNAs were mostly altered to circular forms: both 1-long terminal repeat (1-LTR) and 2-LTR in TNPO3 KD cells. We therefore suggest that TNPO3 is required for successful PFV replication, at least at/after the nuclear entry step of viral DNA. These findings highlight the obscure mysteries of PFV-host interaction and the requirement of TNPO3 for productive infection of PFV in 293T cells.

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

  • Eun-Hye Hong;Jae-Hyoung Song;Seong-Ryeol Kim;Jaewon Cho;Birang Jeong;Heejung Yang;Jae-Hyeon Jeong;Jae-Hee Ahn;Hyunjin Jeong;Seong-Eun Kim;Sun-Young Chang;Hyun-Jeong Ko
    • IMMUNE NETWORK
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    • v.20 no.4
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    • pp.32.1-32.15
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    • 2020
  • Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

Antiviral Activity of Zanthoxylum Species against Influenza Virus (인플루엔자 바이러스에 대한 Zanthoxylum속의 항바이러스 효과 검정)

  • Choi, Hwa-Jung;Song, Jae-Hyoung;Kwon, Dur-Han;Baek, Seung-Hwa;Ahn, Young-Joon
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.4
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    • pp.273-278
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    • 2008
  • We aimed to investigate the antiviral activity of Zanthoxylum species against influenza virus A/WS/33, A/PR/8 and B/Lee/40 used by sulforhodamine B (SRB) assay and the action of leaves extracts of Zanthoxylum piperitum on life cycle of influenza virus A/WS/33. Among the twelve extracts, only the leaf extract of Z. piperitum exhibited strong antiviral activity at low concentration of less than 10${\mu}g/m{\ell}$ with no citotoxicity (50${\mu}g/m{\ell}$) against all of three viruses. In addition, only oseltamivir showed antiviral activity with $IC_{50}$ of 65.3${\mu}g/m{\ell}$ against influenza A/WS/33 among the viruses. Furthermore, the leaf extract of Z. piperitum suppressed infection of influenza virus A/WS/33, when added just prior (-1 hr) or after virus inoculation (0 hr). Leaf extract of Z. piperitum directly affect the infectivity of influenza virus A/WS/33 particles. Therefore, Leaf extract of Z. piperitum exhibited higher antiviral activity against three influenza viruses than that of the oseltamivir, which directly interacts with influenza A/WS/33 particles, affecting the initial stages of infection such as receptor binding and virus entry.

The impact of COVID-19 on human reproduction and directions for fertility treatment during the pandemic

  • Lee, Dayong
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.4
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    • pp.273-282
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    • 2021
  • Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, resulting in a pandemic. The virus enters host cells through angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2). These enzymes are widely expressed in reproductive organs; hence, coronavirus disease 2019 (COVID-19) could also impact human reproduction. Current evidence suggests that sperm cells may provide an inadequate environment for the virus to penetrate and spread. Oocytes within antral follicles are surrounded by cumulus cells, which rarely express ACE2 and TMPRSS2. Thus, the possibility of transmission of the virus through sexual intercourse and assisted reproductive techniques seems unlikely. Early human embryos express coronavirus entry receptors and proteases, implying that human embryos are potentially vulnerable to SARS-CoV-2 in the early stages of development. Data on the expression of ACE2 and TMPRSS2 in the human endometrium are sparse. Moreover, it remains unclear whether SARS-CoV-2 directly affects the embryo and its implantation. A study of the effect of SARS-CoV-2 on pregnancy showed an increase in preterm delivery. Thus, vertical transmission of the virus from mother to fetus in the third trimester is possible, and further data on human reproduction are required to establish this possibility. Based on analyses of existing data, major organizations in this field have published guidelines on the treatment of infertility. Regarding these guidelines, despite the COVID-19 pandemic, reproductive treatment is crucial for the well-being of society and must be continued under suitable regulations and good standard laboratory practice protocols.

M Protein from Dengue virus oligomerizes to pentameric channel protein: in silico analysis study

  • Ayesha Zeba;Kanagaraj Sekar;Anjali Ganjiwale
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.41.1-41.11
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    • 2023
  • The Dengue virus M protein is a 75 amino acid polypeptide with two helical transmembranes (TM). The TM domain oligomerizes to form an ion channel, facilitating viral release from the host cells. The M protein has a critical role in the virus entry and life cycle, making it a potent drug target. The oligomerization of the monomeric protein was studied using ab initio modeling and molecular dynamics simulation in an implicit membrane environment. The representative structures obtained showed pentamer as the most stable oligomeric state, resembling an ion channel. Glutamic acid, threonine, serine, tryptophan, alanine, isoleucine form the pore-lining residues of the pentameric channel, conferring an overall negative charge to the channel with approximate length of 51.9 Å. Residue interaction analysis for M protein shows that Ala94, Leu95, Ser112, Glu124, and Phe155 are the central hub residues representing the physicochemical interactions between domains. The virtual screening with 165 different ion channel inhibitors from the ion channel library shows monovalent ion channel blockers, namely lumacaftor, glipizide, gliquidone, glisoxepide, and azelnidipine to be the inhibitors with high docking scores. Understanding the three-dimensional structure of M protein will help design therapeutics and vaccines for Dengue infection.

The Effects of Border Shutdowns on the Spread of COVID-19

  • Kang, Nahae;Kim, Beomsoo
    • Journal of Preventive Medicine and Public Health
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    • v.53 no.5
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    • pp.293-301
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    • 2020
  • Objectives: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, some countries imposed entry bans against Chinese visitors. We sought to identify the effects of border shutdowns on the spread of the COVID-19 outbreak. Methods: We used the synthetic control method to measure the effects of entry bans against Chinese visitors on the cumulative number of confirmed cases using World Health Organization situation reports as the data source. The synthetic control method constructs a synthetic country that did not shut down its borders, but is similar in all other aspects. Results: Six countries that shut down their borders were evaluated. For Australia, the effects of the policy began to appear 4 days after implementation, and the number of COVID-19 cases dropped by 94.4%. The border shutdown policy took around 13.2 days to show positive effects and lowered COVID-19 cases by 91.7% on average by the end of February. Conclusions: The border shutdowns in early February significantly reduced the spread of the virus. Our findings are informative for future planning of public health policies.

Antiviral Effect of Retro-2.1 against Herpes Simplex Virus Type 2 In Vitro

  • Dai, Wenwen;Wu, Yu;Bi, Jinpeng;Wang, Jingyu;Wang, Shuai;Kong, Wei;Barbier, Julien;Cintrat, Jean-Christophe;Gao, Feng;Jiang, Zhengran;Gillet, Daniel;Su, Weiheng;Jiang, Chunlai
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.849-859
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    • 2018
  • Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

Transcriptional Analysis for Oral Vaccination of Recombinant Viral Proteins against White Spot Syndrome Virus (WSSV) in Litopenaeus vannamei

  • Choi, Mi-Ran;Kim, Yeong-Jin;Jang, Ji-Suk;Kim, Sung-Koo
    • Journal of Microbiology and Biotechnology
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    • v.21 no.2
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    • pp.170-175
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    • 2011
  • This study was carried out for the molecular level identification of recombinant protein vaccine efficacy, by oral feeding against white spot syndrome virus infection, with the comparison of viral mRNA transcriptional levels in shrimp cells. For the determination of WSSV dilution ratio for the vaccination experiment by oral feeding, in vivo virus titration was carried out using different virus dilutions of virus stock ($1{\times}10^2$, $2{\times}10^2$, and $1{\times}10^3$). Among the dilution ratios, $2{\times}10^2$ diluted WSSV stock was chosen as the optimal condition because this dilution showed 90% mortality at 10 days after virus injection. Recombinant viral proteins, rVP19 and rVP28, produced as protein vaccines were delivered in shrimps by oral feeding. The cumulative mortalities of the shrimps vaccinated with rVP19 and rVP28 at 21 days after the challenge with WSSV were 66.7% and 41.7%, respectively. This indicates that rVP28 showed a better protective effect against WSSV in shrimp than rVP19. Through the comparison of mRNA transcriptional levels of viral genes from collected shrimp organ samples, it was confirmed that viral gene transcriptions of vaccinated shrimps were delayed for 4~10 days compared with those of unvaccinated shrimps. Protection from WSSV infection in shrimp by the vaccination with recombinant viral proteins could be accomplished by the prevention of entry of WSSV due to the shrimp immune system activated by recombinant protein vaccines.

Mode of Antiviral Activity of Water Soluble Components Isolated from Elfvingia applanata on Vesicular Stomatitis Virus

  • Eo, Seong-Kug;Kim, Young-So;Oh, Ki-Wan;Lee, Chong-Kil;Lee, Young-Nam;Han, Seong-Sun
    • Archives of Pharmacal Research
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    • v.24 no.1
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    • pp.74-78
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    • 2001
  • A preparation of water soluble components (EA) was made from carpophores of Elfvingia applanata (Pers.) Karst and its in vitro antiviral activity on vesicular stomatitis virus [(Indiana serotype, VSV(IND)] was investigated by plaque reduction assay. EA exhibited potent antiviral activity on VSV(IND) growth and negligible cytotoxicity on Vero cells, 50% effective concentration ($EC_{50}C$/) of 104$ug\textrm\/ml$ and 50% cytotoxic concentration ($CC_{50}C$) of 3,793$ug\textrm\/ml$, respectively. Selectivity index (Sl $CC_{50}C$/$EC_{50}C$) of EA on Vero cell and VSV(IND) was about 36.5. EA did not display either a direct virucidal effect on V5V(IND) or induction of antiviral substance by Vero cells upon its treatment. Thus, the mode of antiviral activity of EA was studied at steps of viral adsorption onto cell. When both EA and virus were added to cell monolayers, titer of cell-free virus in culture supernatant increased in ca. 30-40% compared with that of control group and titer of cell-associated virus was 60-100% higher than that of control group. These results suggested that antiviral activity of EA on VSV(IND) might be due to the hindrance of viral entry to cells at eITher endocytosis or loss of envelope.

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Structural Studies on IRES 4-2 Domain of Foot-and-mouth Disease Virus

  • Kim, Young-Mee;Yoo, Jun-Seok;Cheong, Hae-Kap;Lee, Chul-Hyun;Cheong, Chae-Joon
    • Journal of the Korean Magnetic Resonance Society
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    • v.7 no.2
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    • pp.89-97
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    • 2003
  • Foot-and-mouth disease virus (FMDV) belongs to the aphthovirus genus within the picornavirus which has a single copy of a positive sense RNA. The translation initiation process of FMDV occurs by a cap-independent mechanism directed by a highly structured element (∼435 nt) termed an internal ribosome entry site (IRES). We have designed and prepared FMDV 4-2 RNA (28nt) by in vitro transcription. The 2D NMR data revealed that FMDV 4-2 IRES domain RNA has a flexible loop and bulge conformation. In further study, we need to make an isotope labeled RNA sample and conduct 3D NMR experiments to completely determine the 3D structure. This study may establish a new drug design strategy to treat foot-and mouth disease.

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