INFLUENZA VIRUS INFECTIONS: CLINICAL UPDATE, MOLECULAR BIOLOGY, AND THERAPEUTIC OPTIONS

Influenza is an ancient and deadly disease which has sickened and killed millions of people in local epidemics and global pandemics. Nowadays, it is common knowledge that influenza is a highly infectious viral illness, but before the discovery of viruses the etiological factor of influenza was not known and, therefore, we had to relay solely on the clinical picture characterized by a sudden onset of high fever, cough, headache, muscle and joint pain, unwell feeling, sore throat, and runny nose. These symptoms were clearly described by Hippocrates roughly 2400 years ago, but historical data on influenza were of difficult interpretation, since these symptoms can be similar to those of other respiratory diseases, therefore not distinctive enough. The word Influenza originated in the 15th century from the Italian language, meaning “influence” since the disease was ascribed to unfavorable astrological influences. A different origin could be the word “influsso” for describing the sweating characteristic of the illness or meaning “influence of the cold.” It was not until 1703 when J. Hugger’s thesis submitted at the University of Edinburgh and named “De Catarrho epidemio, vel Influenza, prout in India occidentali sese ostendit” that the Englishspoken world directly associated “influenza” with the disease and its symptoms. After that the name influenza and its shorthand “flu” came into more general use.1 The influenza virus was first isolated from pigs in 1930 by Shope and Lewis.2 This seminal discovery was followed by the isolation in ferrets of influenza A virus by Smith, Andrewes, and Laidlaw.3 In 1936, Burnet demonstrated that influenza virus could be grown in chicken embryonated eggs,4 opening the path for the study of the characteristics of the virus. It is estimated that influenza virus infects every year 5–10% of the adult population worldwide and 20–30% of the children. Even though most patients recover from flu symptoms within a short periodand without serious sequelae, the estimates indicate from 3–5 million cases of serious illness and over 250,000 deaths per year. Therefore, due to its medical importance, influenza viruses have been the focus of extensive research to decipher the molecular mechanisms that dominate cell invasion and pathogenesis