Attenuation of highly pathogenic avian influenza A(H5N1) viruses in Indonesia following the reassortment and acquisition of genes from low pathogenicity avian influenza A virus progenitors

Ni Luh Putu Indi Dharmayanti,Sharmi W Thor,Natosha Zanders,Risza Hartawan,Atik Ratnawati,Yunho Jang,Marisela Rodriguez,David L Suarez,Gina Samaan,Pudjiatmoko Pudjiatmoko,C Todd Davis

doi:10.1038/s41426-018-0147-5

Abstract

The highly pathogenic avian influenza (HPAI) A(H5N1) virus is endemic in Indonesian poultry and has caused sporadic human infection in Indonesia since 2005. Surveillance of H5N1 viruses in live bird markets (LBMs) during 2012 and 2013 was carried out to provide epidemiologic and virologic information regarding viral circulation and the risk of human exposure. Real-time RT-PCR of avian cloacal swabs and environmental samples revealed influenza A-positive specimens, which were then subjected to virus isolation and genomic sequencing. Genetic analysis of specimens collected at multiple LBMs in Indonesia identified both low pathogenicity avian influenza (LPAI) A(H3N8) and HPAI A(H5N1) viruses belonging to clade 2.1.3.2a. Comparison of internal gene segments among the LPAI and HPAI viruses revealed that the latter had acquired the PB2, PB1, and NS genes from LPAI progenitors and other viruses containing a wild type (wt) genomic constellation. Comparison of murine infectivity of the LPAI A(H3N8), wt HPAI A(H5N1) and reassortant HPAI A(H5N1) viruses showed that the acquisition of LPAI internal genes attenuated the reassortant HPAI virus, producing a mouse infectivity/virulence phenotype comparable to that of the LPAI virus. Comparison of molecular markers in each viral gene segment suggested that mutations in PB2 and NS1 may facilitate attenuation. The discovery of an attenuated HPAI A(H5N1) virus in mice that resulted from reassortment may have implications for the capability of these viruses to transmit and cause disease. In addition, surveillance suggests that LBMs in Indonesia may play a role in the generation of reassortant A(H5) viruses and should be monitored.

Highlights

IntroductionVirus, which was first introduced into Indonesia in 2003, is a cause of economically devastating disease in poultry
The highly pathogenic avian influenza (HPAI) A(H5N1)virus, which was first introduced into Indonesia in 2003, is a cause of economically devastating disease in poultry.Since being introduced, the virus has become endemic in the country, causing recurring outbreaks that have resulted in the death of millions of birds due to either infection or the culling of animals
Isolation, and sequencing The Indonesian Research Center for Veterinary Science (IRCVS) in Bogor, Indonesia, collected and analyzed samples obtained during investigations associated with one suspected and two confirmed human influenza A (H5N1) virus infection reports, as well as from the surveillance of active influenza viruses circulating in live bird markets

Summary

Introduction

Virus, which was first introduced into Indonesia in 2003, is a cause of economically devastating disease in poultry. The virus has become endemic in the country, causing recurring outbreaks that have resulted in the death of millions of birds due to either infection or the culling of animals. The majority of A(H5N1) viruses detected in Indonesia most likely descended from a single ancestor derived from clade 2.1 HA9, but as the restrictions on the movement of poultry increased, the introduced viruses evolved independently into those making up the second, third, and fourth order clades (2.1.1, 2.1.2, 2.1.3, 2.1.3.1, 2.1.3.2, 2.1.3.2a, and 2.1.3.2b) on the thousands of islands that comprise the country of Indonesia[10,11]

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