Q & A with Dr. Bhupesh Prusty and Professor Thomas Rudel

Dr. Bhupesh Prusty and Professor Thomas Rudel have published several articles on the phenomenon of ciHHV-6 activation including a study on the interaction between Chlamydia infection and ciHHV-6.  Their recent paper provides further evidence that telomeric shortening can cause the release and subsequent activation of ciHHV-6. Professor Rudel is a well known microbiologist who heads a large laboratory at University of Wuerzburg, Germany that focuses on the pathogenicity of various microorganisms and the interface between infection and cancer. We interviewed Dr. Prusty and Professor Rudel about the implications of these findings, their current studies, and what lies ahead for this team in the field of ciHHV-6 research.

Dr. Bhupesh Prusty and Professor Thomas Rudel

Q: Most of your research has been on Chlamydia infections. What caused you to be interested in HHV-6?

We believe that infections have different consequences on the development of diseases in the presence or absence of other infectious agents. The mechanisms and consequences of co-infections are vastly unexplored. We could establish co-infection of Chlamydia and HHV-6 under laboratory conditions, an important prerequisite to study mechanisms and consequences under defined conditions. Both these pathogens cause widespread infection and persist or maintain lifelong latency in host cells. This represents a fascinating situation to study co-infection of two different pathogens. This is the reason why we started working on HHV-6.

Q: You showed that chlamydia infection induces replication of ciHHV-6. You and Nicola Royle have both shown that ciHHV-6 is associated with shortened telomeres. Do you believe ciHHV-6 individuals with chlamydia infection are at greater risk of developing significant clinical disease?

It is very likely but clinical studies are required to prove an increased infection or disease risk for these ciHHV-6 individuals. We are still characterizing the clinical significance of viral reactivation without forming any infectious viral particles. Such “abortive” viral activity might modify host cell physiology that either directly or by reactivation of other latent pathogens may result in human diseases.

Chlamydia infection induces telomere shortening as well as ciHHV-6 reactivation without infectious viral particle formation. Hence reactivated cells have two clinically significant situations, which can definitely alter the host cell physiology and can allow further disease development.

Q: Do you believe it is advisable for ciHHV-6 individuals to ask their physicians about treatment for Chlamydia infection to avoid in vivo reactivation of ciHHV-6?

Most physicians who are knowledgeable about Chlamydia infection feel it is very important to treat the infection. Treatment can help prevent chronic and persistent infection that causes serious health problems. For example, Chlamydia trachomatis infection, unfortunately, does not cause symptoms in more than 50% of the female patients. These patients are at a very high risk to develop persistent Chlamydia infection. Persistent Chlamydia retains several basic functions, which can reactivate integrated viral genomes.

Q: Should individuals with ciHHV6 monitor antibody levels for possible chlamydia infection?

Yes, monitoring chlamydia (whether by antibody titers or PCR) in these individuals would provide important information on a connection of ciHHV-6 reactivated by chlamydial infection. Under clinical conditions of viral reactivation, one should definitely look for chlamydia infection.

Q: Would you speculate on the consequences, if any, for cancer?

Reactivated viral genome can re-integrate into the same or other chromosomes and may thereby induce genomic instability. Chlamydia infection itself also induces DNA damage. As a consequence, the presence of both Chlamydia and ciHHV-6 may well influence the progression of cancer in these patients. However, so far all data about these infections and telomere shortening have been obtained in cellular infection models. Any prognosis without solid clinical data is not reliable and has to be handle with caution.

Q: What are your future-plans to study integrated HHV6 and chlamydia pneumonia?

We are focusing on bacterial effector proteins that affect the host cell telomere maintenance machinery and induce telomere alteration leading to viral reactivation. We are also perusing global host cell transcriptome and proteome profiling to understand the molecular basis for the resulting disease condition.