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

Authors: DHARMAYANTI, NI LUH PUTU IND - Indonesian Agency For Agricultural Research And Development; THOR, SHARMI - Centers For Disease Control And Prevention (CDC) - United States; ZANDERS, NATOSHA - Centers For Disease Control And Prevention (CDC) - United States; HARTAWAN, RISZA - Indonesian Agency For Agricultural Research And Development; RATNAWATI, ATIK - Indonesian Agency For Agricultural Research And Development; JANG, YUNHO - Indonesian Agency For Agricultural Research And Development; Rodriguez, Marisela; Suarez, David; SAMAAN, GINA - Australian National University; PUDJIATMOKO - Minister Of Agriculture; DAVIS, C. TODD - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: Emerging Microbes & Infections
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/2018
Publication Date: 8/22/2018
Citation: Dharmayanti, N., Thor, S.W., Zanders, N., Hartawan, R., Ratnawati, A., Jang, Y., Rodriguez, M., Suarez, D.L., Samaan, G., Pudjiatmoko, Davis, C. 2018. Attenuation of highly pathogenic avian influenza A (H5N1) viruses in Indonesia following reassortment and acquisition of genes from low pathogenicity avian influenza (LPAI) A virus progenitors. Emerging Microbes & Infections. 7(1):1-14. https://doi.org/10.1038/s41426-018-0147-5.
DOI: https://doi.org/10.1038/s41426-018-0147-5

Interpretive Summary: Avian influenza virus can cause serious problems in the poultry industry. The virus in chickens can be characterized by viruses that cause high mortality, referred to as highly pathogenic avian influenza (HPAI), or those that cause little to no mortality in chickens, referred to as low pathogenic avian influenza (LPAI). In Indonesia they have had HPAI of the H5 subtype circulating in the country since 2003, and more recently they identified a LPAI H3 virus also circulating in poultry. Influenza viruses have 8 short gene segments, and these gene segments can be swapped between viruses when they infect the same host. This study describes the detection of avian influenza viruses in Indonesia that had swapped genes and the characterization of those viruses. One H5 virus was attenuated when they infected mice with no mortality after infection. These changes in the virus may affect how these viruses persist in the environment and may affect transmission. Additional surveillance in Indonesia is needed to track these unique viruses.

Technical 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.