Neutrophils May Be a Vehicle for Viral Replication and Dissemination in Human H5N1 Avian Influenza

Abstract

The mechanism of systemic spread of H5N1 virus in patients with avian influenza is unknown. Here, H5N1 nucleoprotein and hemagglutinin were identified by immunohistochemistry in the nucleus and cytoplasm of neutrophils in the placental blood of a pregnant woman. Viral RNA was detected in neutrophils by in situ hybridization and enhanced real-time polymerase chain reaction. Therefore, neutrophils may serve as a vehicle for viral replication and transportation in avian influenza.

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

“…Neutrophils exposed to influenza virus undergo activation of the respiratory burst, followed by depression of cell function when subsequently exposed to secondary stimuli (69), although innate defense proteins of the collectin family have been shown to protect neutrophils from these depressive effects (70). Neutrophils themselves have been reported as both nonpermissive (6) and susceptible to influenza virus infection (71,72) and to respond to virus exposure via TLR7-and/or TLR8-mediated production of proinflammatory cytokines (71). Neutrophil granules, including azurophil/primary, secondary, and secretory granules, contain an array of molecules with potential for antiviral activity, including ␣ and ␤ defensins and pentraxins, which have been shown to exert antiviral activities against a range of viruses, including influenza (73)(74)(75).…”

Neutrophils: Neglected Players in Viral Diseases

“…The ability of neutrophils to internalize viruses was investigated by confocal microscopy (Mohamadzadeh et al, 2006), PCR (Larochelle et al, 1998;Gerna et al, 2000;Zhao et al, 2008), flow cytometry (Hufford et al, 2012), and immunochemistry (Zhao et al, 2008) to detect the presence of viral-associated molecules and particles (Hackemann et al, 1974;Larochelle et al, 1998). The development of green fluorescent protein-tagged viruses also allowed the visualization of internalized viruses (Duffy et al, 2012;Hufford et al, 2012).…”

“…While murine neutrophils are not susceptible to influenza virus (Tate et al, 2011) and alphavirus (Levitt et al, 1979) infections, human neutrophils are susceptible to these viruses (Abramson et al, 1982b(Abramson et al, , 1986Zhao et al, 2008) and others, such as MARV (Mohamadzadeh et al, 2006), EpsteinBarr virus (EBV) (Larochelle et al, 1998), and RSV (Halfhide et al, 2011). Viruses may enter human neutrophils by endocytosis or phagocytosis.…”

“…Viruses may enter human neutrophils by endocytosis or phagocytosis. However, with the exception of MARV (Mohamadzadeh et al, 2006), active replication for EBV (Larochelle et al, 1998), RSV, and influenza virus (Cassidy et al, 1988;Zhao et al, 2008) was presented. Therefore, virus infection in neutrophils could either facilitate virus clearance and control disease progression, or it may exacerbate disease manifestations.…”

Role of Fat-Soluble Vitamins A and D in the Pathogenesis of Influenza: A New Perspective

“…e mechanism of systemic spread of H5N1 virus in patients with avian in�uenza is unknown. Based on immunohistochemical �ndings of H5N1 nucleoprotein and hemagglutinin in the nucleus and cytoplasm of neutrophils in the placental blood of a pregnant woman, it was suggested that neutrophils could serve as a vehicle for viral replication and transportation in avian in�uenza [166].…”