Apoptosis and Pathogenesis of Avian Influenza A (H5N1) Virus in Humans

Mongkol Uiprasertkul; Rungrueng Kitphati; Pilaipan Puthavathana; Romchat Kriwong; Alita Kongchanagul; Kumnuan Ungchusak; Suwimon Angkasekwinai; Kulkanya Chokephaibulkit; Kanittar Srisook; Nirun Vanprapar; Prasert Auewarakul

Disclosures

Emerging Infectious Diseases. 2007;13(5):708-712. 

In This Article

Abstract and Introduction

Abstract

The pathogenesis of avian influenza A (H5N1) virus in humans has not been clearly elucidated. Apoptosis may also play an important role. We studied autopsy specimens from 2 patients who died of infection with this virus. Apoptosis was observed in alveolar epithelial cells, which is the major target cell type for the viral replication. Numerous apoptotic leukocytes were observed in the lung of a patient who died on day 6 of illness. Our data suggest that apoptosis may play a major role in the pathogenesis of influenza (H5N1) virus in humans by destroying alveolar epithelial cells. This pathogenesis causes pneumonia and destroys leukocytes, leading to leukopenia, which is a prominent clinical feature of influenza (H5N1) virus in humans. Whether observed apoptotic cells were a direct result of the viral replication or a consequence of an overactivation of the immune system requires further studies.

Introduction

The pathogenesis of avian influenza A (H5N1) virus in humans is not well understood. Although several studies have shown some aspects of this pathogenesis in animal models, direct evidence of pathogenic mechanisms in humans has been limited to only a few autopsy studies.[1,2,3] We previously demonstrated in an autopsy case that alveolar epithelial cells are the major target cell type of this virus.[3] The case in that study, as well as other previous autopsy reports, died late in the disease. Some of the findings may not reflect the actual pathogenesis at the acute period but may be consequences of secondary events. We performed an autopsy of a patient who died on day 6 of onset of illness. The findings in this case are more likely to reflect viral pathogenesis in the acute phase of the disease.

Apoptosis has been implicated in the pathogenesis of influenza. Infection of epithelial cells and lymphocytes has been shown to induce apoptosis in vitro.[4,5,6,7,8] Several modes of apoptosis induction and responsible viral genes have been proposed.[8,9,10,11,12,13] Infection with virulent influenza (H5N1) virus was also shown to induce lymphopenia and lymphocyte apoptosis in vivo.[14] However,whether and to what extent apoptosis contributes to the highly virulence property of influenza (H5N1) viruses are not clear. In this report, we studied apoptotic activity in 2 patients who died of avian influenza.

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