Apoptosis of hepatocytes caused by punta toro virus (Bunyaviridae: Phlebovirus) and its implication for phlebovirus pathogenesis

Xiaohua Ding, Fangling Xu, Hongli Chen, Robert B. Tesh, Shu Yuan Xiao

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Experimental infection of hamsters with Punta Toro virus (PTV) produces a disease with clinical and pathological similarities to the severe human hemorrhagic fever caused by Rift Valley fever virus (RVFV), thus providing an animal model for RVFV pathogenesis. In this model, hepatocytic apoptosis is the main pathological component of liver injuries that are responsible for severe hemorrhagic manifestations. To further elucidate whether viral replication in hepatocytes directly causes apoptosis, we studied the morphological and biochemical changes of apoptosis in HepG2 cells at different time points after PTV infection. Cellular viability began to decrease 12 hours after infection compared with controls. Caspases 3/7 were activated significantly at 48 and 72 hours after infection, and phosphatidylserine translocation and DNA fragmentation were also detected at 48 and 72 hours. Cell cycle analysis by flow cytometry showed that infected HepG2 cells were arrested at G 0/G1 phase. Furthermore, virus titer increased with apoptosis progression, suggesting that viral replication is necessary for the apoptotic process. These results indicate that PTV infection alone, without a secondary inflammatory cellular reaction, induces hepatocytic apoptosis and suggest that future therapeutics for RVFV hemorrhagic disease might target inhibition of cellular apoptotic pathways during the acute infection.

Original languageEnglish (US)
Pages (from-to)1043-1049
Number of pages7
JournalAmerican Journal of Pathology
Volume167
Issue number4
StatePublished - Oct 2005

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Phlebovirus
Bunyaviridae
Rift Valley fever virus
Hepatocytes
Apoptosis
Viruses
Virus Diseases
Hep G2 Cells
Infection
Caspase 7
Phosphatidylserines
G1 Phase
DNA Fragmentation
Viral Load
Caspase 3
Cricetinae
Cell Cycle
Flow Cytometry
Fever
Animal Models

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Apoptosis of hepatocytes caused by punta toro virus (Bunyaviridae : Phlebovirus) and its implication for phlebovirus pathogenesis. / Ding, Xiaohua; Xu, Fangling; Chen, Hongli; Tesh, Robert B.; Xiao, Shu Yuan.

In: American Journal of Pathology, Vol. 167, No. 4, 10.2005, p. 1043-1049.

Research output: Contribution to journalArticle

Ding, Xiaohua ; Xu, Fangling ; Chen, Hongli ; Tesh, Robert B. ; Xiao, Shu Yuan. / Apoptosis of hepatocytes caused by punta toro virus (Bunyaviridae : Phlebovirus) and its implication for phlebovirus pathogenesis. In: American Journal of Pathology. 2005 ; Vol. 167, No. 4. pp. 1043-1049.
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