A pathological study revealing the expression of M gene segment of influenza A virus determines host range. According to the study, the host range of the influenza A virus (IAV) is restricting by dysregulating expression of the M viral gene segment. IAV pandemics arise when a virus adapting to a non-human host overcomes species barriers to successfully infect humans and sustain human to human transmission.
But to gauge the adaptive potential and therefore pandemic risk posed by a particular IAV, it is critical to understand the mechanisms underlying viral adaptation to human hosts. To address this question, Lowen and Steel examined the role of one of IAV’s eight gene segments, the M segment, in host adaptation. The authors compared the growth of IAVs with avian and human-derived M segments in avian and mammalian systems.
The expression of M gene
The M segment restricted viral growth and transmission specifically in mammalian cells. This host-specific restricting growth was associating with excess production of the M2 protein; resulting from transcription of the avian IAV M segment in mammalian cells. Excess production of the M2 protein interfered with cellular functions on which the virus relies.
When present at high levels, M2 had marked effects on the infected cell; blocking the turnover of autophagic vesicles and redirecting LC3B II, the activated form of a critical autophagy mediator; to the plasma membrane. These effects were finding to rely on the proton channel activity of M2; and occurring when either the avian or human M2 protein was over expressing in the infecting cells.
Effects on the infected cell
Influenza A virus (IAV) pandemics arise when a virus adapted to a non-human host; overcomes species barriers to successfully infect humans and sustain human to human transmission. To gauge the adaptive potential and therefore pandemic risk posed by a particular IAV; it is critical to understand the mechanisms underlying viral adaptation to human hosts. Importantly, the reduction in viral growth conferring by avian M segments in mammalian systems; could be attributing at least in part to disruption of vesicular homeostasis and was fully attributing to the altering expression levels of M1 and M2.
However, the results suggest that control of M segment gene expression is a critical aspect of IAV host adaptation. According to the authors; the findings could lead to the development of effective strategies for monitoring IAV pandemic risk. The results reveal that careful regulation of viral gene expression is achieving through species-specific interactions with the host cell; and thereby point to this aspect of the viral life cycle as a restriction on avian influenza A virus emergence in humans.