The History of Human Metapneumovirus (HMPV)
Human metapneumovirus (HMPV) is a significant human respiratory pathogen that was first described in 2001 by Dutch virologists. This virus is a leading cause of acute respiratory infection. HMPV was discovered in stored nasopharyngeal samples from children experiencing respiratory illness. Although newly discovered, serological evidence suggests that HMPV, or a very close relative, has been circulating in the human population since at least 1958. This highlights an important point: despite being identified relatively recently, HMPV has a "hidden" history in the human population, likely spanning several decades. HMPV is a negative-sense single-stranded RNA virus belonging to the Pneumoviridae family, closely related to the avian metapneumovirus (AMPV) subgroup C. It was the second most common cause of acute respiratory tract illness in children under 5 in a large US outpatient clinic as of 2016. This article provides a comprehensive overview of the history of HMPV, including its origin, evolution, major outbreaks, impact on human health, current status, and future outlook.
Origin of HMPV
HMPV is closely related to avian metapneumovirus (AMPV), specifically AMPV subgroup C. This close relationship suggests that HMPV likely evolved from AMPV-C following a zoonotic transfer, meaning it originated in birds and then spread to humans. The virus was initially isolated using the RAP-PCR (RNA arbitrarily primed PCR) technique. Analysis of metapneumovirus sequences suggests this spill-over event may have occurred approximately 200 years ago. While the exact origin remains unclear, it is hypothesized that the virus originated from birds.
Evolution of HMPV
Since its discovery, HMPV has been identified in countries on all continents except Antarctica. Phylogenetic analyses have shown that HMPV is most closely related to APV serotype C. The estimated rate of mutation for HMPV is 7.12 × 10⁻⁴ substitutions per site per year. This relatively high mutation rate has potential implications for the virus's ability to adapt and evolve, potentially leading to increased viral diversity and posing challenges for vaccine development. The estimated time to the most recent common HMPV ancestor is 97 years (with a 95% likelihood range of 66-194 years). Analysis suggests that HMPV diverged from AMPV-C approximately 269 years ago (with a 95% likelihood range of 106-382 years).
Currently, HMPV is divided into two main genotypes, A and B, which are further classified into subgroups. Viral subtypes are groups of viruses within a species that have distinct genetic characteristics. These subtypes can have different levels of virulence, transmissibility, and responses to treatment. Understanding the different subtypes of HMPV is crucial for tracking the spread of the virus and developing effective prevention and control strategies. The following table summarizes the known subtypes of HMPV:
Recently, novel subtypes A2c, A2b1, and A2b2 have been proposed. Subtypes A2b1 and A2b2 appear to have diverged from subtype A2b about a decade after subtype A2 was divided into subtypes A2a and A2b. These findings are crucial for understanding the evolutionary patterns of HMPV and for future surveillance and epidemiological studies.
Major Outbreaks of HMPV
HMPV typically causes seasonal outbreaks, with a higher prevalence during the winter and spring months. However, there have been instances of significant increases in HMPV cases outside of the typical seasonal patterns. For example, in late winter and spring of 2023, a notable surge in HMPV cases occurred in New South Wales (NSW), Australia, with over 1000 cases reported.
More recently, an increase in HMPV cases, particularly in China, has raised concerns. In 2024, China reported 327 HMPV cases, a 45% increase compared to 2023. This rise in cases has led to crowded hospitals and increased pressure on the healthcare system. Amidst this rising concern, the first documented case of HMPV in India was reported in an 8-month-old baby in Bengaluru. This case, occurring in early January 2025, highlights the global spread of the virus.
Apart from China, other countries, including Malaysia, have also reported a rise in HMPV cases. In India, two cases of HMPV were reported in Bengaluru in early January 2025. These cases were identified through routine surveillance, and the infected individuals had no recent travel history, suggesting local transmission.
Impact of HMPV on Human Health
HMPV primarily affects the respiratory system, causing symptoms similar to the common cold, such as cough, fever, nasal congestion, and shortness of breath. Usually, these symptoms are mild and resolve within 2-5 days. However, HMPV can sometimes cause more severe lower respiratory infections, including bronchiolitis, bronchitis, and pneumonia. According to the U.S. Centers for Disease Control and Prevention (CDC), HMPV is associated with approximately 20,000 hospitalizations among children under 5 in the U.S. every year. Young children, older adults, and individuals with weakened immune systems are at higher risk of developing severe complications.
HMPV infection can also exacerbate existing respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Studies have shown that HMPV may play a role in the initiation and progression of asthma. In rare cases, HMPV infection can lead to hospitalization and even death, particularly in vulnerable populations.
Current Status of HMPV
HMPV is now recognized as a globally circulating respiratory virus, with seasonal outbreaks occurring worldwide. The recent increase in cases, particularly in China, has highlighted the need for continued surveillance and public health awareness. While HMPV is not considered a new pandemic threat, its impact on public health, especially among vulnerable populations, warrants attention.
Future Outlook of HMPV
The future outlook for HMPV involves ongoing research to better understand the virus's evolution, transmission dynamics, and impact on human health. The development of effective vaccines and antiviral treatments is crucial for preventing and managing HMPV infections, especially in high-risk groups. Continued surveillance and public health measures, such as handwashing and respiratory hygiene, are essential to control the spread of HMPV.
Conclusion
HMPV is a common respiratory virus that has been circulating in the human population for decades, even though it was only relatively recently identified in 2001. While typically causing mild cold-like symptoms, HMPV can lead to severe respiratory complications in vulnerable individuals, including young children, older adults, and those with weakened immune systems. The recent increase in cases, particularly in China, reminds us of the ongoing challenges in controlling HMPV and the need for continued vigilance.
The genetic diversity of HMPV, highlighted by its relatively high mutation rate and the emergence of new subtypes, poses challenges for developing effective vaccines and antiviral treatments. Therefore, a multifaceted approach is needed to mitigate the impact of HMPV on human health. This approach should include ongoing research to better understand the virus's evolution and transmission dynamics, continued surveillance to monitor outbreaks and identify high-risk populations, and public health measures to promote respiratory hygiene and prevent the spread of infection. By combining these strategies, we can work towards effectively managing HMPV and protecting vulnerable populations from its potentially severe consequences.
