Influenza: lessons from past pandemics, warnings from current incidents

Abstract

Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and in humans (through direct contact with infected birds) have had important economic repercussions and have raised concerns that a new influenza pandemic will occur in the near future. The eradication of pathogenic avian influenza viruses seems to be the most effective way to prevent influenza pandemics, although this strategy has not proven successful so far. Here, we review the molecular factors that contribute to the emergence of pandemic strains.

The influenza virus RNA synthesis machine

“…Transfer of some of these viruses to humans, or transfer of genes from avian to human influenza viruses, originated the influenza pandemics and caused the establishment of new lineages of human viruses. 1,4 Indeed, sporadic cases of highly pathogenic H5N1 avian influenza in humans continue to occur since 2003 and pose a risk for the origin of a devastating new pandemic (http://www.who.int/csr/ disease/avian_influenza/en/).…”

“…Later pandemics appeared in 1957 and 1968 and the most recent one started in 2009. 1,2 Influenza type A viruses, members of the Orthomyxoviridae family, cause most of these epidemics and all pandemics. They constitute an extremely heterogeneous virus population comprising many subtypes, which are defined as any combination of their surface glycoproteins, haemaglutinin (HA) and neuraminidase (NA).…”

Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

“…Influenza A viruses, causing acute infections, continuously escape from recognition by virus neutralizing Ab as a result of accumulation of mutations in their surface glycoproteins hemagglutinin and neuraminidase (antigenic drift) or by introduction of new subtypes of these glycoproteins (antigenic shift) [2,3]. Recent outbreaks of highly pathogenic avian influenza A virus infections in poultry and in humans have raised concerns that a new influenza pandemic will occur in the near future [4]. Thus, prediction of the severity of continuously emerging human influenza virus strains remains a high public health priority, but it is limited by our incomplete understanding of the molecular determinants of pathogenicity in this disease.…”

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

“…It is widely believed that the emergence of a new influenza pandemic caused by avian strains is only a matter of time and that a safe, effective and easily manufactured vaccine is required [1][2][3]. Pandemic H5N1 vaccine candidates tested to date were manufactured using attenuated reassortant viruses.…”