Wednesday, July 10, 2024

Frontiers: Phylogenetic and Mutational Analysis of H10N3 Avian Influenza A virus in China: Potential Threats to Human Health



China has often been described as the `cradle of influenza', primarily because human, avian, and swine influenza viruses circulate there more-or-less year round, population densities are very high, and because humans and farm animals there often have opportunities to come in close contact.
During the 20th century, 2 of the 3 major influenza pandemics (1957 Asian Flu, 1968 Hong Kong Flu) originated from this region. Additionally, the highly pathogenic `Asian’ version of H5N1 emerged from China in the mid-1990s,  they saw the emergence of avian H7N9 epidemic in 2013, and in 2014 they reported the first of (now > 90) H5N6 spillover events. 

Over the past dozen years we've also seen scattered reports of other zoonotic viruses in the region, including a number of H10 viruses.  H10N8 emerged in late 2013 infecting at least 3 people, and last winter we saw the first known human infection with H10N5.

In June of 2021 China's NHC Reported the 1st Human H10N3 Avian Flu Infection - Jiangsu Province), followed in 2022 by A Cryptic Report of A 2nd H10N3 Case from Hong Kong's CHP.  Last April a 3rd case was reported from Yunnan Province (see Nature Portfolio preprint).

Today we've an updated report from the same authors on the genetic changes seen in this latest H10N3 case, and their potential threat to human health.  

The authors describe finding 4 mutations of varying concern in this latest case, along with the patient's treatment and course of illness. 

Due to its length, I've only posted some excerpts. Follow the link to read it in its entirety.  I'll have a brief postscript after the break. 

Phylogenetic and mutational analysis of H10N3 avian influenza A virus in China: potential threats to human health

Jingyi Dai1†‡ Jun Zhao2†‡ Jiawei Xia1† Pei Zhang1‡ Yadi Ding1‡ Qiujing Li1‡ Min Hou3 Xianhui Xiong3 Qianqi Jian3 Yanyan Liu3 * Guiming Liu1*

In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. This study focuses on a patient infected with the H10N3 subtype of avian influenza virus, admitted to the Third People’s Hospital of Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase chain reaction (PCR) analysis were conducted on the patient’s sputum, confirming the H10N3 infection. 

The patient presented severe pneumonia symptoms such as fever, expectoration, chest tightness, shortness of breath, and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase (NA) genes of the virus showed that the virus was most closely related to a case of human infection with the H10N3 subtype of avian influenza virus found in Zhejiang Province, China. Analysis of amino acid mutation sites identified four mutations potentially hazardous to human health.

Consequently, this underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing advanced genomic surveillance techniques.


A previously healthy 51-year-old male experienced recurrent fever for a week, reaching a maximum temperature of 39°C, accompanied by symptoms of cough, expectoration, chest tightness, and shortness of breath. Despite seeking medical attention at the local community health service center, his symptoms did not significantly improve. Consequently, he was transferred to the Department of Respiratory and Critical Care Medicine at the Third People’s Hospital of Kunming City in Yunnan Province, Southwest China, on March 6, 2024.

Upon admission (7 days after the onset of illness), the patient presented with a temperature of 39℃, a pulse rate of 110 beats per minute, a respiratory rate of 28 breaths per minute, oxygen saturation of 78%, and blood pressure measuring 105/70 mmHg (Table 1). Laboratory tests revealed a low white blood cell count, elevated neutrophil percentage, decreased platelet count, and elevated levels of infectious markers. Additionally, a throat swab specimen tested positive for influenza A virus nucleic acid by PCR (Table 2). Chest computed tomography (CT) revealed multiple patchy and increased density shadows in both lungs, characterized by unclear boundaries and uneven density (Figure 1). The initial diagnosis upon admission included severe pneumonia, type I respiratory failure, and influenza attributed to influenza A virus.
The patient was administered oseltamivir (150mg, twice daily) and methylprednisolone (80mg, once daily) and corresponding antibiotics for treatment. Subsequent sputum culture results revealed infection with Candida albicans and Staphylococcus epidermidis and Acinetobacter joni and Carbapenem-resistant Enterobacter cloacae, prompting the administration of appropriate antibiotics (Table 1). The patient’s fever subsided on March 17th (18 days after illness onset), and on March 19th (20 days after illness onset), the nucleic acid test for influenza A virus returned negative results for the first time.
Subsequent test results on March 21st (22 days after illness onset) indicated normalization of the patient’s white blood cell count, along with a decrease or return to normal levels of infection markers. However, the patient exhibited prolonged prothrombin time. Chest computed tomography scans showed a reduction in lesions compared to previous scans (Figure 1). The lung lesions were noticeably absorbed, and there was no chest tightness or dyspnea. The patient was discharged on April 17th, and home oxygen therapy was recommended.



The clinical manifestations of avian influenza A virus infection vary depending on the virus subtypes involved. For instance, infection with H5N1 and H7N9 subtypes can lead to severe pneumonia and related complications in patients. Conversely, certain subtypes such as H7 and H9 may only induce conjunctivitis or mild respiratory symptoms (Liu et al., 2013). It’s important for healthcare providers to be aware of these differences in clinical presentation when diagnosing and managing cases of avian influenza virus infection. As of now, only two cases of human infection with the H10N3 subtype have been reported. The symptoms observed in the patient infected with H10N3 in this case closely resemble those documented in the two previously known cases of H10N3 infection. Notably, all cases resulted in severe pneumonia in the affected patients (Qi et al., 2022; Zhang et al., 2023).

However, the molecular features of these cases are different, and our case has some different mutations. The Q226L mutation makes the virus more adept at binding to human α-2,6-sialic acid receptors, significantly increasing the likelihood of human infection (Shi et al., 2014). The mutation D701N in the PB2 protein has been shown to enhance the replication activity of avian influenza RNA polymerase within the human body. This mutation also increases the adaptability and pathogenicity of the virus to the human host, potentially serving as a crucial factor in avian influenza viruses crossing the host species barrier (Li et al., 2005).

The presence of the S409N mutation in the PA protein suggests the potential for infectivity in humans and may contribute to increased pathogenicity of this particular virus strain (Finkelstein et al., 2007). The S31N mutation in the M2 protein has been associated with resistance to adamantanes, a class of antiviral drugs (Pielak et al., 2009). This mutations in the protein of the Yunnan H10N3 virus strain underscores the potential for increased threat posed by H10N3 in humans. Therefore, it is imperative to closely monitor the dynamics of this subtype.

The case of human infection with H10N3 avian influenza A virus highlighted in this study involved close contact with live birds, particularly through the handling and slaughtering of dead birds. Although there is no direct evidence, it is likely that this exposure eventually resulted in the patient contracting avian influenza and experiencing severe illness.

This underscores the importance of paying special attention to instances of unexpected bird deaths and promptly reporting such cases. Moreover, it emphasizes the necessity of establishing a comprehensive avian influenza surveillance system, not only within Yunnan but also globally, to continuously and vigilantly monitor the H10N3 virus strain and its potential impact on human health.

         (Continue . . . )


Although we've only seen a limited number of human H10 cases from China, its spread in wild birds - and reassortment with H9N2 viruses - have raised concerns for years.  A few previous blogs include:

A reminder that nature's laboratory is open 24/7, and while we are focused primarily on HPAI H5N1, there may well be others in the queue.