Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar 15;398(2):243-50.
doi: 10.1016/j.virol.2009.11.041. Epub 2010 Jan 12.

Simian TRIM5alpha proteins reduce replication of herpes simplex virus

Natalia Reszka  1 , Changhong Zhou, Byeongwoon Song, Joseph G Sodroski, David M Knipe
Affiliations

Simian TRIM5alpha proteins reduce replication of herpes simplex virus

Natalia Reszka et al. Virology. .

Abstract

Old World monkey TRIM5alpha proteins are known to block the replication of human immunodeficiency virus and other retroviruses in a species-specific fashion. In this report, we show that specific forms of simian TRIM5alpha proteins can restrict herpes simplex virus (HSV) infection. To define the effect of TRIM5alpha on HSV replication, we examined HSV infection in HeLa cell lines that stably express simian and human orthologs of TRIM5alpha proteins. We demonstrated that several simian TRIM5alpha proteins can restrict HSV replication, with the TRIM5alpha protein of rhesus macaques showing the strongest inhibition of HSV infection. We also found that the level of the inhibition of virus replication was viral strain-specific. TRIM5alpha is likely to inhibit HSV at the early stage of infection; however, at later times of infection, the levels of TRIM5alpha are significantly decreased. Thus, some TRIM5alpha proteins exhibit antiviral effects that extend beyond retroviral infections, but HSV may be able to reduce this restriction by reducing TRIM5alpha levels during the later phases of virus replication. Our results also argue that TRIM5alpha is only part of the reduced level of HSV replication in rhesus macaques, which are known to be less susceptible to HSV infection than other primates.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Replication of HSV-1 KOS strain (A) and HSV-2 186 syn+ strain (B) in HeLa and rhesus macaque fibroblast cell lines. HeLa or rhesus macaque fibroblast cells were infected with HSV-1 or HSV-2 at an MOI of 3 PFU/cell. Total virus was harvested at the times indicated, and yields were determined by plaque assay on Vero cells.
Figure 2
Figure 2
Effect of rhesus monkey TRIM5α protein on HSV replication at different multiplications of infection. H-R cells that express rhesus monkey TRIM5α or the H-L control cells were infected with HSV-1 KOS strain (panel A) or with HSV-2 186 syn+ strain (panel B) at an MOI of 1, 3, 10 or 30 PFU/cell. The infections were harvested at 24 hpi, and viral yields were measured by plaque assay on Vero cells.
Figure 3
Figure 3
HSV-2 yields obtained from cell lines that stably express different TRIM5α variants. H-R (rhesus monkey), H-H (human), H-AGM (African green monkey), H-Sq (squirrel monkey) and H-L (control empty vector) cells were infected with HSV-2 186 syn+ strain at an MOI of 3 PFU/cell and harvested after 24 h. Viral yields were measured on Vero cells.
Figure 4
Figure 4
Effect of rhesus TRIM5α protein on HSV-1 and HSV-2 protein synthesis as measured by Western blots. A: H-R and H-L cells infected with HSV-1 KOS strain at an MOI of 3 PFU/cell or mock-infected. The cells were harvested at the times indicated, and viral protein expression was analyzed by Western blotting using anti-ICP4, ICP27 and ICP8 antibodies. B: H-R and H-L cell lines infected with HSV-2 186 syn+ strain or mock infected. The cells were harvested at the times indicated, and viral protein expression was analyzed by Western blotting using anti-ICP27 and ICP8 antibodies. β-actin served as the loading control.
Figure 5
Figure 5
Effect of rhesus TRIM5α on replication of different HSV-2 and HSV-1 strains. (A) Infection of H-R cells with HSV-2 strains: HSV 2-G strain, SD90/3P strain or the HSV-2 laboratory strain 186 syn+. H-R cells that stably express rhesus monkey TRIM5α or the control H-L cells were infected with HSV-2 186 syn+, G, or SD90/3P strains at an MOI of 3. The infections were harvested at 24 hpi, and viral yields were measured by plaque assay on Vero cells. (B) Infections with HSV-1 strains. H-R cells that express rhesus monkey TRIM5α or the control H-L cells were infected with HSV-1 strains F and 17syn+ at an MOI of 3. The infections were harvested at 24 hpi, and the viral yields were measured by plaque assay on Vero cells.
Figure 6
Figure 6
Localization of ICP0 in infected cells. H-L control cells (panel 1) or cells that expressed rhesus (panel 2) or human (panel 3) TRIM5α were mock-infected (panel A) or infected with HSV-1 KOS strain (panel B and C) and stained for ICP0 at 4 and 8 hpi.
Figure 7
Figure 7
Localization of TRIM5α and ICP0 in infected cells. Cells that expressed rhesus monkey or human TRIM5α were infected with HSV-1 KOS strain and stained for TRIM5α (green) and ICP0 (red) at 4 hpi.
Figure 8
Figure 8
Levels of TRIM5α in cells infected with HSV-1 or HSV-2. The H-R or H-L cells were infected with HSV-1 KOS strain (panel A) or HSV-2 186 syn+ strains (panel B) at an MOI of 3 PFU/cell or mock–infected. The infected cells were harvested at the times indicated, and Western blots were performed to detect TRIM5α.
Figure 9
Figure 9
Levels of different TRIM5α proteins in cells infected with HSV-2 186 syn+ strain. The H-R, H-H, H-AGM, H-S and H-L cell lines were infected with HSV-2 186 syn+ strain at an MOI of 3 PFU/cell or mock–infected. The infected cells were harvested at 4 or 6 hpi. The resulting lysates were resolved by SDS-PAGE and a Western blot was performed with anti ICP8 and HA antibodies. β-actin served as the loading control.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Asper M, Sternsdorf T, Hass M, Drosten C, Rhode A, Schmitz H, Günther S. Inhibition of different Lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus. J Virol. 2004;78:3162–9. - PMC - PubMed
    1. Barouch DH. Challenges in the development of an HIV-1 vaccine. Nature. 2008;455:613–9. - PMC - PubMed
    1. Björndal AS, Szekely L, Elgh F. Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML) protein in cultured cells. BMC Microbiol. 2003;3:6. - PMC - PubMed
    1. Blondel D, Regad T, Poisson N, Pavie B, Harper F, Pandolfi PP, De Thé H, Chelbi-Alix MK. Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies. Oncogene. 2002;21:7957–70. - PubMed
    1. Bonilla WV, Pinschewer DD, Klenerman P, Rousson V, Gaboli M, Pandolfi PP, Zinkernagel RM, Salvato MS, Hengartner H. Effects of promyelocytic leukemia protein on virus-host balance. J Virol. 2002;76:3810–8. - PMC - PubMed

Publication types