Bat Influenza A

Little yellow-shouldered bat "Sturnira lilium"[1]

Introduction

a. Bat ecology and virology Bats are known to play a crucial role as reservoir hosts of many zoonotic viruses. Zoonotic viruses are currently the biggest concern for emerging infections in humans. As of 2012, 75% of emerging infectious diseases was due to zoonoses. Bats host a large variety of viruses, including lyssaviruses, filoviruses, coronaviruses, and henipaviruses. Bats carry these viruses without being affected by the symptoms, unlike many other mammals. Bats also have far-reaching and overlapping migratory ranges, making intraspecies viral transfer a large factor in their ability to host and spread viruses (Wong et al., 2006).
b. Influenza A virology

a. Guatemala

A study done by Tong et al. in 2009-2010 revealed that bats could be a potential reservoir host for influenza A virus. They collected a total of 316 bats from 21 different species across 8 locations in southern Guatemala. They took oral and rectal swab samples from each bat. To test the hypothesis that these bats might harbor influenza viruses, Tong et al. developed a pan-influenza virus RT-PCR that detects the catalytic subunit of RNA polymerase, the polymerase basic protein (PB1). PB1 is one of the most conserved proteins within RNA viruses. By running a PCR reaction with this PB1 RT-PCR primer, they searched for novel influenza viruses within the bat’s genomes. Tong et al. found that three of the 316 bat rectal swab samples, all from the “little-yellow shouldered bat” (Sturnia lilium), were positive for influenza virus. The three samples contained 105-106 viral genome copies per 100 μL of rectal swab suspension, indicating a positive result. Two of the positive samples were captured in 2009 in El Jobo, Guatemala, and the third was captured in 2010 from Agüero, Guatemala (about 50 km away). The viral genomes from the two infected bats GU09-153 and GU09-164 were practically identical to each other (99.99% nucleotide identity). However, they were more distantly related to the infected bat found a year later in Agüero, Guatemala (96.1% nucleotide identity). This shows that the genome of this bat influenza has the potential to change over time and within individual bats. Tissue samples (liver, intestine, and kidney) taken from the infected bats all tested positive for viral influenza A material, but the oral swab samples tested negative. Tang et al. hypothesizes that this difference in viral material location means that the influenza virus spreads through the bat in an infectious process, compared to orally ingesting infected material. Since the viral material was found within the rectum of the bats, it is most likely that the virus can be contracted through contact with infected bat feces (Tong et al., 2012).
By aligning the nucleotide sequences of known crucial influenza A components, such as hemagglutin (HA), polymerase (PA), neuraminidase (NA), and nucleoprotein (NP), with the bat influenza viral genome, the identity of the bat virus could be determined. Tong et al. (2012) found that each of the genomic segments could be aligned to known influenza A virus genome sequences with little to no gaps, with the exception of the NA sequence, which needed 16 gaps to align with influenza A virus. From this data, Tong et al. concluded that the influenza virus discovered in bats in Guatemala is structurally closely related to influenza A. In order to classify the subtype of influenza A that these bats host, Tong et al. investigated the genome of the HA protein. By using BLAST, it was found that, on average, the bat virus HA gene has 45% amino acid sequence identity to all HAs from all known influenza A subtypes. In contrast, by looking at the relatedness of NA genes between bat and human influenza A genomes, the bat NA protein only has 24% amino acid sequence identity to other influenza A NA subtypes. The NA protein is involved in the sialic acid-binding/catalytic site, which is how the virus binds to target cells. From this data, Tong et al. concluded that this influenza A virus found is a new subtype, designated as H17. They also concluded that the virus has a different mechanism of infection, and does not use sialic acid-binding sites to bind to target cells. (Tong et al., 2012).

b. Peru

Another study done by Tong et al. in 2010 identified another novel influenza A virus, named H18N11, from a flat-faced fruit bat (Artibeus planirostris) in Truenococha, Peru. The intestine tissue from this bat specimen tested strongly positive for influenza virus, while the other tissues tested negative. A phylogenetic analysis comparing the influenza A genome between the Guatemala and Peru bats showed that the viruses are closely related, but there is a distinct lineage between them.

Potential for human infection

The detection of this virus in 1% of the total bat population tested in Guatemala is similar to the frequency of influenza virus detection in wild bird populations, which are known to transmit influenza to humans (Munster et al., 2007)

a. Viral genetic reassortment

For both H17 and H18 influenza

b. Structural differences between bat and human influenza A

By investigating the crucial structural components of influenza A and comparing their genes to the bat influenza virus, it was concluded by Tang et al. (2012) that the bat virus

i. HA proteins ii. Sialic acid receptor binding

Munster VJ, et al. (2007) Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds. PLoS Pathog 3:e61

Suxiang Tong, Yan Li, Pierre Rivailler, Christina Conrardy, Danilo A. Alvarez Castillo, Li-Mei Chen, Sergio Recuenco, James A. Ellison, Charles T. Davis, Ian A. York, Amy S. Turmelle, David Moran, Shannon Rogers, Mang Shi, Ying Tao, Michael R. Weil, Kevin Tang, Lori A. Rowe, Scott Sammons, Xiyan Xu, Michael Frace, Kim A. Lindblade, Nancy J. Cox, Larry J. Anderson, Charles E. Rupprecht and Ruben O. Donis. A distinct lineage of influenza A virus from bats. PNAS 2012, 109 (11): 4269-4274. (http://www.pnas.org/content/109/11/4269.long)

Tong Suxaing, Zhu Xueyong, Shi Mang, Zhang Jing, Bourgeois Melissa, Yang Hua, Chen Xianfeng, Recuenco Sergio, Gomez Jorge, Chen Li-Mei, Johnson Adam, Tao Ying, Dreyfus Cyrille, Yu Wenli, McBride Ryan, Carney Paul J., Gilbert Amy T., Chang Jessie, Guo Zhu, Davis Charles, Paulson James C., Stevens James, Rupprecht Charles E., Holmes Edward C., Wilson Ian A., Donis Ruben O., New World Bats Harbor Diverse Influenza A Viruses. PLOS: Pathogens. October 10, 2013. 9(10): e1003657. (http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003657)

Wong, S., Lau, S., Woo, P., Yuen, K. Y. Bats as a continuing source of emerging infections in humans. 2006. Rev. Med. Virol. 17: 67-91.