10^th International Virology Summit July 02-04, 2018 Vienna, Austria

Biography:

 

Abstract:

Hantavirus cardiopulmonary syndrome is characterized by pulmonary capillary leakage and alveolar flooding, resulting in 50% mortality due to fulminant hypoxic respiratory failure. In addition, depression of cardiac function ensues, which complicates the picture with cardiogenic shock. Early diagnosis and appropriate use of extracorporeal membrane oxygenation (ECMO) are amongst the lifesaving interventions in this fatal illness. Annually 150,000-200,000 cases of hantavirus infections are reported worldwide, and there is no treatment for this viral illness. There is an urgent need for the development of a vaccine and antiviral therapeutics to improve the prognosis of this deadly disease. The hantaviral genome is composed of three negative sense genomic RNA segments: S, M and L that encode nucleocapsid protein (N protein), glycoproteins (Gn and Gc) and viral RNA dependent RNA polymerase (RdRp), respectively. We showed that hantaviruses have evolved a novel translation initiation mechanism, operated by N protein, that preferentially favors the translation of viral mRNA in the infected host cell. N protein simultaneously binds to a highly conserved triplet repeat sequence of the viral mRNA 5’ UTR and the 40S ribosomal subunit via the ribosomal protein S19 (RPS19). The simultaneous binding selectively loads the N protein associated ribosomes on viral transcripts and boosts their translation by avoiding the competition from host cell transcripts for the same translation apparatus. Using a high throughput screening assay we screened a chemical library of 100,000 chemical compounds to identify molecules that interrupt the N protein mediated translation strategy. Using this approach, we identified three lead inhibitors that selectively bind to N protein; inhibit N protein–UTR interaction and shutdown the N protein mediated translation strategy without affecting the canonical translation machinery of the host cell. The lead inhibitors are well tolerated by cells and their selective interruption in viral protein synthesis dramatically inhibits hantavirus replication. These inhibitors hold promise for the development of first anti-hantaviral therapeutic that will be of paramount importance in reducing disease mortality in hantavirus infected patients. 

 

Biography:

Mohammad Mir did his PhD from Saha Institute of Nuclear Physics, Department of Atomic Energy of India in 2003. He then Moved to University of New Mexico for his Postdoctoral training in Virology, where he worked with hemorrhagic fever viruses. He then joined the University of Kansas, School of Medicine as Assistant Professor in Virology in the year 2009. In 2015, he joined the Western University of Health Sciences, California, as Associate Professor in Virology. His research program at Western University is focused on replication and therapeutic intervention of emerging negative strand RNA viruses.       

 

Abstract:

Long term study of pathology in different viral infections allows dividing them into 4 groups. 1. Acute and chronic infections with highly specific histopathological changes due to viral inclusions and/or very typical cell transformations (in our experience herpes, influenza, cytomegaly etc). 2. Acute or chronic infections with typical cell’s changes and tissue reactions, but additional verification are needed (in our experience HIV, HBV, HCV, enteroviruses, parvovirus, JCV, HPV etc) 3. Chronic infections causing inflammation but without (or at least not yet known) typical morphological changes (in our experience EBV, HHV6, 7, 8). 4. Viral latency or incorporation in host genome without any changes at light microscopy (CMV, EBV etc). In many cases while investigating surgical material pathologist may contribute in identification of etiology of disease (in our experience hepatitis, encephalitis, lymphadenopathy and placentitis of unclear etiology). During study of liver biopsies in viral hepatitis and placenta certain prognostic and predictive criteria have been elaborated. Pathological studies have to determine immediate death causes; we had the opportunity to analyze them in HIV infection, viral hepatitis B and C, influenza. Histopathological studies contribute in complex studies of pathogenesis of viral infection, especially their quite different clinical course. Another highly important but very rarely discussed issue is peculiarities of viral lesions in different organs and tissues; we have data related to brain and placenta. Very important issue of quite different mixed infections can’t be successfully studied without taking in consideration the results of special morphological investigation. Most interesting data can be obtained if we are able to analyze structural changes in different material (surgical, autoptic, experimental) providing correlations with clinical, virological, molecular biological, genetic, epidemiological data. In many cases we can go forward only using modern technologies such as IHC, hybridization and PCR in situ, electron microscopy.