hCMV ja APOBECK3A (2017)

 2018,   28.11.
 https://www.spandidos-publications.com/10.3892/mmr.2016.4778

Human cytomegalovirus RL13 protein interacts with host NUDT14 protein affecting viral DNA replication

NUDT14 proteiini on UDPG pyrofosfataasi, joka hydrolysoi UDPG:n tuottaen Glc-1-P ja UMP. 

RL13 on  ihmisen CMV:n myöhäisiä proteiineja ja tekemällä interaktion  NUDT14:n kanssa se  vähentää  NUDT14 proteiinia,  mikä edistää  virus DNA:n kopioita, NUDT14 ylössäätäminen ei kuitenkaan vaikuttanut  virus DNA:n määrään. 

 2017

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686750/

J Virol. 2017 Dec 1; 91(23): e01296-17.

Published online 2017 Nov 14. Prepublished online 2017 Sep 27. doi:  10.1128/JVI.01296-17

PMCID: PMC5686750

PMID: 28956761

APOBEC3A Is Upregulated by Human Cytomegalovirus (HCMV) in the Maternal-Fetal Interface, Acting as an Innate Anti-HCMV Effector

Yiska Weisblum,^a,b,c Esther Oiknine-Djian,^a,b,c Zichria Zakay-Rones,^b Olesya Vorontsov,^a,b,c Ronit Haimov-Kochman,^d Yuval Nevo,^e David Stockheim,^f Simcha Yagel,^d Amos Panet,^b and Dana G. Wolf^a,c

Jae U. Jung, Editor

Jae U. Jung, University of Southern California;

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ABSTRACT

Human cytomegalovirus (HCMV) is the leading cause of congenital infection and is associated with a wide range of neurodevelopmental disabilities and intrauterine growth restriction. Yet our current understanding of the mechanisms modulating transplacental HCMV transmission is poor. The placenta, given its critical function in protecting the fetus, has evolved effective yet largely uncharacterized innate immune barriers against invading pathogens. Here we show that the intrinsic cellular restriction factor apolipoprotein B editing catalytic subunit-like 3A (APOBEC3A [A3A]) is profoundly upregulated following ex vivo HCMV infection in human decidual tissues—constituting the maternal aspect of the placenta. We directly demonstrated that A3A severely restricted HCMV replication upon controlled overexpression in epithelial cells, acting by a cytidine deamination mechanism to introduce hypermutations into the viral genome. Importantly, we further found that A3 editing of HCMV DNA occurs both ex vivo in HCMV-infected decidual organ cultures and in vivo in amniotic fluid samples obtained during natural congenital infection. Our results reveal a previously unexplored role for A3A as an innate anti-HCMV effector, activated by HCMV infection in the maternal-fetal interface. These findings pave the way to new insights into the potential impact of APOBEC proteins on HCMV pathogenesis.