Small Rho GTPases and cholesterol biosynthetic pathway intermediates in african swine fever virus infection

Jose I. Quetglas, Bruno Hernáez, Inmaculada Galindo, Raquel Muñoz-Moreno, Miguel A. Cuesta-Geijo, Covadonga Alonso

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The integrity of the cholesterol biosynthesis pathway is required for efficient African swine fever virus (ASFV) infection. Incorporation of prenyl groups into Rho GTPases plays a key role in several stages of ASFV infection, since both geranylgeranyl and farnesyl pyrophosphates are required at different infection steps. We found that Rho GTPase inhibition impaired virus morphogenesis and resulted in an abnormal viral factory size with the accumulation of envelope precursors and immature virions. Furthermore, abundant defective virions reached the plasma membrane, and filopodia formation in exocytosis was abrogated. Rac1 was activated at early ASFV infection stages, coincident with microtubule acetylation, a process that stabilizes microtubules for virus transport. Rac1 inhibition did not affect the viral entry step itself but impaired subsequent virus production. We found that specific Rac1 inhibition impaired viral induced microtubule acetylation and viral intracellular transport. These findings highlight that viral infection is the result of a carefully orchestrated modulation of Rho family GTPase activity within the host cell; this modulation results critical for virus morphogenesis and in turn, triggers cytoskeleton remodeling, such as microtubule stabilization for viral transport during early infection.

Original languageEnglish
Pages (from-to)1758-1767
Number of pages10
JournalJournal of Virology
Volume86
Issue number3
DOIs
StatePublished - Feb 2012
Externally publishedYes

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