Department of Virology

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Research Group

Research Projects

Research in our department focuses on several viruses that target immune and respiratory regions, as well as prions that target the central nervous system. We seek to understand the mechanisms by which these pathogens replicate and induce pathogenesis, and to apply our understanding to the development of methods to control these agents, remove them from blood products, and diagnosis their infection rapidly.

(1) Infections to the immune system
Dengue illness, which is transmitted to humans by mosquitoes, is among the most important viral infectious diseases in tropical and subtropical regions around the world. There are four antigenically distinct dengue virus serotypes. Severe dengue cases, such as dengue hemorrhagic fever and dengue shock syndrome, mostly occur by secondary infection with a serotype different from the primary infected serotype. Although individuals infected with dengue virus produce high titers of neutralizing antibodies, some of these antibodies may play a role in the antibody-dependent enhancement of the secondarily infected serotype, which could make vaccine development difficult. We seek to characterize the mechanism by which dengue virus derived from South Asian countries induces dengue illness in order to develop an antidengue viral drug. For its in vivo evaluation, we are also developing animal models for dengue viral infection. In addition, we are preparing human monoclonal antibodies to understand the viral-induced pathogenicity and to develop therapeutic antibodies.

(2) Infections to the respiratory system
Influenza virus induces typical acute infection in the respiratory region. In addition to seasonal influenza viruses, a swine-origin pandemic virus appeared in 2009. Currently, the possible global emergence of a pandemic virus from highly pathogenic avian influenza virus, such as H5N1, is a public concern worldwide. Together with Alexandria University, we are studying H5N1 circulating in Egypt. Recently, we found that some of the new H5 sublineages in Egypt have acquired an enhanced binding capacity to human-type receptors. The purpose of our search is to ascertain the pandemic potential of these H5N1 viruses in Egypt. We have prepared several human neutralizing monoclonal antibodies against influenza virus. Because the epitope region recognized by one of the monoclonal antibodies is highly conserved and forms a conformational structure, we are working on the possible development of a new vaccine with this conformation in the synthetic peptide in collaboration with several companies.

(3) Blood-borne infections
We are working to establish how to remove infectious agents, such as parvovirus B19, SARS-corona virus, hepatitis E virus, and prions, from blood products in collaboration with a company.

(4) Rapid diagnosis kits
There are many techniques for the diagnosis of viral infections, including immunofluorescence, ELISA, Western blot, and PCR assays. We are currently working with several companies towards the development of rapid diagnosis kits against several infectious diseases.

Fig.1 Fig.2
Dengue virus is produced as a single polyprotein and is cleaved into 10 proteins for viral replication. The dengue virus protease complex, which is essential for cleavage, is composed of the NS3 protease and NS2B cofactor. Small molecules that interfere with the interaction between NS2B and NS3 impair protease activity and inhibit viral replication. NS2B (frame structure) interacts with the pocket site of NS3 (green). The key residues of NS3 that interact with the newly developed small compound are indicated in pink.


Dengue viral infection induces strong humoral immunity and antibody production. These antibodies include neutralizing antibodies and negatively regulating antibodies by antibody-dependent enhancement. Human monoclonal antibodies are being prepared by using immune cells from patients to investigate dengue virus-induced pathogenicity and to develop antibody therapeutics.

Fig.4 Fig.5
Some of the new H5 sublineages in Egypt have acquired an increased attachment to and infectivity in the human lower respiratory tract (H5N1 virus attached to human tracheal epithelia is stained red in the panel). We are currently investigating the mechanism(s) underlying the possible emergence of pandemic H5N1 viruses in Egypt and its risk in the field, in collaboration with Alexandria University. (a) Pathology of the classical virus lineage (H5N1) in humans. The virus lineage only has binding affinity for α2,3 sialylglycan and needs to reach the lower respiratory tract.
(b) Pathology of the new H5 sublineage that has emerged in Egypt. Expansion of receptor usage (increased α2,6 sialylglycan binding) enables the new sublineage to bind more efficiently to epithelia in the lower respiratory tract.

Major publications

  1. Yasugi M, Nakamura S, Daidoji T, Ramadhany R, Yang C-S, Yasunaga T, Iida T, Horii T, Ikuta K, Takahashi K, Nakaya T. Frequency of D222G and Q223R hemagglutinin mutants of pandemic (H1N1) 2009 influenza virus in Japan between 2009 and 2010. PLoS One 2012;7(2):e30946. Epub 2012 Feb 17.
  2. Watanabe Y, Ibrahim MS, Suzuki Y, Ikuta K. The changing nature of avian influenza A virus (H5N1). Trends Microbiol. 2012 Jan;20(1):11-20. Epub 2011 Dec 5.
  3. Watanabe Y, Ibrahim MS, Ellakany HF, Kawashita N, Mizuike R, Hiramatsu H, Sriwilaijaroen N, Takagi T, Suzuki Y, Ikuta K. Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt. PLoS Pathog. 2011 May:7(5):e1002068. Epub 2011 May 26.
  4. Mizuike R, Sasaki T, Baba K, Iwamoto H, Shibai Y, Kosaka M, Kubota-Koketsu R, Yang CS, Du A, Sakudo A, Tsujikawa M, Yunoki M, Ikuta K. Development of two types of rapid diagnostic test kits to detect the hemagglutinin or nucleoprotein of the swine-origin pandemic influenza A virus H1N1. Clin. Vaccine Immunol. 2011 Mar;18(3):494-9. Epub 2011 Jan 12.
  5. Kurosu T, Khamlert C, Phanthanawiboon S, Ikuta K, Anantapreecha S. Highly efficient rescue of dengue virus using a co-culture system with mosquito/mammalian cells. Biochem Biophys Res Commun. 2010 Apr 2;394(2):398-404. Epub 2010 Mar 7.


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