Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.

Airborne transmission of influenza A/H5N1 virus between ferrets

Four 'antigenic sites' on the three-dimensional structure of the influenza haemagglutinin are identified. At least one amino acid substitution in each site seems to be required for the production of new epidemic strains between 1968 and 1975.

/pdf/structural-identification-of-the-antibody-binding-sites-of-hkaf38yj86.pdf

Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation

Three worldwide (pandemic) outbreaks of influenza occurred in the 20th century: in 1918, 1957, and 1968. The latter 2 were in the era of modern virology and most thoroughly characterized. All 3 have been informally identified by their presumed sites of origin as Spanish, Asian, and Hong Kong influenza, respectively. They are now known to represent 3 different antigenic subtypes of influenza A virus: H1N1, H2N2, and H3N2, respectively. Not classified as true pandemics are 3 notable epidemics: a pseudopandemic in 1947 with low death rates, an epidemic in 1977 that was a pandemic in children, and an abortive epidemic of swine influenza in 1976 that was feared to have pandemic potential. Major influenza epidemics show no predictable periodicity or pattern, and all differ from one another. Evidence suggests that true pandemics with changes in hemagglutinin subtypes arise from genetic reassortment with animal influenza A viruses.

/pdf/influenza-pandemics-of-the-20th-century-3u1iuqbuh4.pdf

Influenza Pandemics of the 20th Century

Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.

/pdf/approved-antiviral-drugs-over-the-past-50-years-4if2c1n8se.pdf

Approved Antiviral Drugs over the Past 50 Years

Influenza viruses are significant human respiratory pathogens that cause both seasonal, endemic infections and periodic, unpredictable pandemics. The worst pandemic on record, in 1918, killed approximately 50 million people worldwide. Human infections caused by H5N1 highly pathogenic avian influenza viruses have raised concern about the emergence of another pandemic. The histopathology of fatal influenza virus pneumonias as documented over the past 120 years is reviewed here. Strikingly, the spectrum of pathologic changes described in the 1918 influenza pandemic is not significantly different from the histopathology observed in other less lethal pandemics or even in deaths occurring during seasonal influenza outbreaks.

The Pathology of Influenza Virus Infections

Influenza: Observations on the Recovery of Virus from Man and on the Antibody Content of Human Sera

The filtration of herpes virus through graded collodion membranes

The role of coagulase in staphylococcal infections.

Influenza infection of man from the ferret

The Nature and Mode of Action of Staphylococcus Coagulase.

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