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Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins
Published on: August 31, 2017
Simian TRIM5alpha proteins reduce replication of herpes simplex virus
Natalia Reszka1, Changhong Zhou, Byeongwoon Song
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
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.
Insights
Certain simian TRIM5alpha proteins restrict herpes simplex virus (HSV) replication. Rhesus macaque TRIM5alpha shows strong inhibition, but HSV may evade this antiviral defense by lowering TRIM5alpha levels.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Old World monkey TRIM5alpha proteins are recognized for their species-specific restriction of retroviral replication, including human immunodeficiency virus.
- The broader antiviral capabilities of TRIM5alpha beyond retroviruses remain incompletely understood.
Purpose of the Study:
- To investigate the potential of simian TRIM5alpha proteins to restrict herpes simplex virus (HSV) infection.
- To define the specific TRIM5alpha orthologs and viral strains affected by this restriction.
Main Methods:
- Utilized HeLa cell lines engineered for stable expression of various simian and human TRIM5alpha proteins.
- Assessed the impact of TRIM5alpha expression on HSV replication dynamics and viral strain specificity.
Main Results:
- Several simian TRIM5alpha proteins demonstrated significant restriction of HSV replication.
- The TRIM5alpha protein from rhesus macaques exhibited the most potent inhibition of HSV infection.
- The degree of viral replication inhibition was dependent on the specific HSV strain.
- TRIM5alpha appears to inhibit HSV during early infection stages, with levels decreasing later in the replication cycle.
Conclusions:
- Simian TRIM5alpha proteins possess antiviral activity against herpes simplex virus, extending their known function beyond retroviruses.
- Herpes simplex virus may counteract TRIM5alpha restriction by downregulating its levels during later infection phases.
- TRIM5alpha contributes to the inherent resistance of rhesus macaques to HSV, though it is not the sole factor.
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