Idiopathic pulmonary fibrosis (IPF) and herpesvirus saimiri: an interview with Elazar Rabbani, Chief Executive Officer of Enzo

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What is idiopathic pulmonary fibrosis (IPF) and what was previously thought to cause this disease?

Pulmonary fibrosis is a condition where fibrotic or scarred tissue progressively develops in the lungs. In some cases the particular cause is known but in others it remains unknown and is given the term “idiopathic”.

Idiopathic pulmonary fibrosis is a severe chronic disease that leads to loss of lung function where the median survival is two-to-three years after diagnosis.

Currently there are no drugs that have been found to have appreciable value in treating the disease and ultimately the only means available becomes a lung transplant.

Attempts to find a causative agent have been extensive but fruitless with some suspicions being cast towards members of the herpes virus family that are human pathogens. However, these studies have been controversial where further work showed no link or only a weak correlation for any particular herpesvirus that has been investigated.

What are herpesviruses and where does the herpesvirus saimiri come from?

Herpesviruses are large double-stranded DNA viruses. Some common diseases that are the result of herpes infections include oral (cold sores) and genital sores by Herpes simplex; chicken pox early in life and shingles in more mature adults from varicella zoster; Burkitts lymphoma and Epstein-Barr virus; and principally in AIDS patients, Kaposi’s sarcoma from KSHV infection.

The recent study broadened the investigative field to look at a virus (herpesvirus saimiri) that is not normally considered to be a pathogen of humans, but rather was known to be endemic but non-pathogenic in a South American monkey called the squirrel monkey.

Although this monkey is the natural host, an early small study looking at antibodies in humans had shown that in 100 human samples, four of them were reactive towards herpesvirus saimiri antigens, although there were no known exposures of these individuals to squirrel monkeys.

Could you please outline the recent study looking at the association of IPF and the presence of the herpesvirus saimiri? What sparked this research and what did it involve?

The recent study has used DNA probes derived from numerous portions of the herpesvirus saimiri genome and found an exceedingly strong correlation where in tissue specimens from 21 individual IPF patients, every single one was positive with the viral probes.

The negative correlation was equally impressive where fibrotic lung specimens from patients without IPF were all negative with the DNA probes. These non-IPF specimens included lung cancer, emphysema, pneumonitis and viral infections from measles, adenovirus, hantavirus or rotavirus.

The potential for infection of IPF patients with herpesvirus saimiri was derived from a previous publication that had discovered expression of a cytokine called IL-17 in IPF patients. This was an unusual finding since expression was seen in epithelial cells, and this particular gene is usually only expressed in blood cells as part of the immune defense.

Its connection with herpesvirus saimiri was with regard to the presence of analogues of human genes that are coded by herpes genomes where each herpesvirus has a particular set of these analogues. However, the only herpesvirus that is currently known to code for expression of IL-17 is herpesvirus saimiri.

What were the main findings of this study?

The major finding of the study is the extremely strong correlation of the presence of the Herpesvirus saimiri sequences in IPF patients and its absence in non-IPF patients. Previous studies with other herpesviruses that found some level of viral infection in IPF were seriously weakened by the finding of essentially similar infection levels in non-IPF patients.

Did your research determine whether this correlation was causal or is further investigation needed to establish this?

At this point it is too early to determine if this result is causal or a result of the presence of IPF, but the extremely high correlation level seen for the presence of the virus seems to indicate it’s a causative agent.

In addition, it had previously been seen that infection of certain strains of mice by a related herpesvirus called MHV-68 could induce a pulmonary fibrosis condition that is often used as an animal model of IPF, so the potential for herpesvirus saimiri being a causative agent is very high. To answer your question, further investigation will be needed.

What impact do you think this discovery will have?

The impact of this discovery covers many areas. In the first place, the diagnosis of IPF is similar to that of lupus; you start by eliminating what it isn’t. After all of the other potential disorders that might be responsible for lung fibrosis have been eliminated, IPF is left as a diagnosis.

Confirmation of the diagnosis as IPF is usually only achieved in a positive sense by high-resolution, computerized tomography, an expensive and elaborate procedure. Thus there has been a long-standing need for a simple and direct test for diagnosis of IPF that can now be achieved either by looking for an inappropriate expression of IL-17 or herpesvirus saimiri nucleic acids in biopsy specimens. It’s also possible that less invasive tests such as lung lavage or blood tests may be developed.

Another major point is that IPF is always discovered at a late stage where lung function has already been severely compromised. The development of simpler less invasive tests will potentially create the ability to detect the disease earlier in patients who would ultimately develop the disease. This may lead to therapeutic processes that are more effective.

In addition, it should be noted that in some cases, development of therapeutic regimes may only have a capacity to block progression and not reverse damage that has already developed. As such, earlier intervention may stop events at a stage prior to the start of a loss of lung function.

Lastly, the identification of a viral target opens a wide window of opportunity to develop therapeutic regimes, both in terms of interruptions in the viral life cycles through in vitro systems and using new animal models.

Do you think it will be possible to cure IPF one day?

The possibilities of a cure are certainly there, just as the discovery of HIV in the development of AIDS has allowed development of therapeutic regimes that stabilize a patient and limit progression of the disease and inspired ongoing efforts to eliminate the virus from AIDS patients.

What are Enzo’s plans for the future?

Enzo is working on the isolating the viral genomes from the IPF patient samples and obtaining nucleic acid sequences. This will allow development of nucleic acid-based detection systems that are currently very successful in detection and quantification of viral pathogens, such as hepatitis B virus, hepatitis C virus and HIV.

As noted above, the development of these assays could allow earlier detection of IPF and it will also provide a simple means of monitoring the success of any therapeutic regime being tested out in patients.

Where can readers find more information?

More information about IPF can be found out at websites provided by the Coalition for Pulmonary Fibrosis (www.coalitionforpf.org) and the Pulmonary Fibrosis Foundation (www.pulmonaryfibrosis.org).

About Elazar Rabbani

Elazar-Rabbani-Big-ImageDr. Elazar Rabbani, Ph.D., is Enzo Biochem's founder and has served as the company's Chairman of the Board and Chief Executive Officer since its inception in 1976 and Secretary since November 25, 2009.

Dr. Rabbani has authored numerous scientific publications in the field of molecular biology, in particular, nucleic acid labeling and detection. He is also the lead inventor of many of Enzo’s pioneering patents covering a wide range of technologies and products.

Dr. Rabbani received his Bachelor of Arts degree from New York University in Chemistry and his Ph.D. in Biochemistry from Columbia University. He is a member of the American Society for Microbiology.

About Enzo Biochem

Enzo Biochem is a pioneer in molecular diagnostics, leading the convergence of clinical laboratories, life sciences and therapeutics through the development of unique diagnostic platform technologies that provide numerous advantages over previous standards.

A global company, Enzo Biochem utilizes cross-functional teams to develop and deploy products systems and services that meet the ever-changing and rapidly growing needs of health care both today and into the future.

Underpinning Enzo Biochem’s products and technologies is a broad and deep intellectual property portfolio, with patent coverage across a number of key enabling technologies.

April Cashin-Garbutt

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April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.

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