Differential transcriptional responses between human primary macrophages and dendritic cells identified transmembrane serine protease 13 (TMPRSS13) as a novel host dependency factor for Zika virus infection.

Dr Chu, Hin   (Principal Investigator (PI))

Dr Chan Jasper Fuk Woo   (Co-Investigator)

Professor Yuen Kwok Yung   (Co-Investigator)

36

2020-10-01

996285

Differential transcriptional responses between human primary macrophages and dendritic cells identified transmembrane serine protease 13 (TMPRSS13) as a novel host dependency factor for Zika virus infection.

dendritic cells, dependency host factor, macrophages, TMPRSS13, Zika virus

Virology,Infection/Parasitology

Biology and Medicine (M)

17123920

General Research Fund (GRF)

2020

On-going

1 Objective 1: To understand the fundamental biology of TMPRSS13 in the context of ZIKV infection. Extending from our pilot studies on the identification of TMPRSS13 as a novel host dependency factor for efficient ZIKV replication, we aim to thoroughly dissect the role of TMPRSS13 on ZIKV infection in this proposal. In Objective 1, we first seek to understand the basic biology of TMPRSS13 in the context of ZIKV infection. 2 Objective 1 (A) First, we will characterize the baseline expression of TMPRSS13 in un-infected cells. Objective 1 (B) Second, we will investigate the cellular localization of TMPRSS13. Objective 1 (C) Third, we will evaluate the expression pattern of TMPRSS13 upon ZIKV infection. 3 Objective 2: To thoroughly investigate the impact of TMPRSS13 on ZIKV infection. Based on the knowledge obtained from Objective 1, we will have a more systemic grasp on the basic biology of TMPRSS13 that is relevant to ZIKV infection. In Objective 2, we will thoroughly investigate the modulatory effect of TMPRSS13 on ZIKV infection on multiple dimensions. 4 Objective 2 (A) First, we will extent our line of investigation on loss of function studies. Objective 2 (B) Second, we will study the outcome of TMPRSS13 overexpression in more details. Objective 2 (C) Third, we will investigate if TMPRSS13 can also modulate the replication of other flaviviruses. 5 Objective 3: To dissect the mechanism of how TMPRSS13 modulate ZIKV replication. Extending from our findings from Objective 1 and 2, we next plan to investigate the mechanism of how TMPRSS13 facilitates ZIKV replication in Objective 3. 6 Objective 3 (A) First, we will examine the role of TMPRSS13 during ZIKV entry. Objective 3 (B) Second, we will investigate if TMPRSS13 mediates cleavage of ZIKV proteins. Objective 3 (C) Third, we will directly assess the association of the cleavage activity of TMPRSS13 with TMPRSS13-facilitated ZIKV replication. Objective 3 (D) Forth, the relative effect of furin and TMPRSS13 on prM cleavage will be assessed. Objective 3 (E) Fifth, the potential effect of additional TMPRSS on prM proteins of flaviviruses will be examined.