Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25552713
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Human cytomegalovirus exploits interferon-induced transmembrane proteins to
facilitate morphogenesis of the virion assembly compartment
#MMPMID25552713
Xie M
; Xuan B
; Shan J
; Pan D
; Sun Y
; Shan Z
; Zhang J
; Yu D
; Li B
; Qian Z
J Virol
2015[Mar]; 89
(6
): 3049-61
PMID25552713
show ga
Recently, interferon-induced transmembrane proteins (IFITMs) have been identified
to be key effector molecules in the host type I interferon defense system. The
invasion of host cells by a large range of RNA viruses is inhibited by IFITMs
during the entry step. However, the roles of IFITMs in DNA virus infections have
not been studied in detail. In this study, we report that human cytomegalovirus
(HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of
the virion assembly compartment (vAC) during infection of human fibroblasts. We
found that IFITMs were expressed constitutively in human embryonic lung
fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in
the later stages of infection. Overexpression of an IFITM protein in MRC5 cells
slightly enhanced HCMV production and knockdown of IFITMs by RNA interference
reduced the virus titer by about 100-fold on day 8 postinfection, according to
the findings of a virus yield assay at a low multiplicity of infection. Virus
gene expression and DNA synthesis were not affected, but the typical round
structure of the vAC was not formed after the suppression of IFITMs, thereby
resulting in defective virion assembly and the production of less infectious
virion particles. Interestingly, the replication of herpes simplex virus, a human
herpesvirus that is closely related to HCMV, was not affected by the suppression
of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a
specific pathway required for HCMV replication. IMPORTANCE: HCMV is known to
repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to
facilitate its replication. Our results expand the range of ISGs that can be
exploited by HCMV for its replication. This is also the first report of a
proviral function of IFITMs in DNA virus replication. In addition, whereas
previous studies showed that IFITMs modulate virus entry, which is a very early
stage in the virus life cycle, we identified a new function of IFITMs during the
very late stage of virus replication, i.e., virion assembly. Virus entry and
assembly both involve vesicle transport and membrane fusion; thus, a common
biochemical activity of IFITMs is likely to be involved. Therefore, our findings
may provide a new platform for dissecting the molecular mechanism of action of
IFITMs during the blocking or enhancement of virus infection, which are under
intense investigation in this field.
free
free
free
