An Animal Model for Chronic Fatigue Syndrome?
http://www.seattlechildrens.org/research/science-industry-partnerships/partnership-opportunities/hhv-human-herpesvirus/
Virology. 2014 Dec;471-473:126-40. doi: 10.1016/j.virol.2014.10.008. Epub 2014 Oct 31.
Discovery and biological characterization of two novel pig-tailed macaque homologs of HHV-6 and HHV-7.
Abstract
Human herpesvirus-6 (HHV-6) and -7 (HHV-7) are Roseoloviruses within the Betaherpesvirus family, which have a high prevalence and suspected involvement in a number of diseases. Using CODEHOP-based PCR, we identified homologs of both viruses in saliva of pig-tailed macaques, provisionally named MneHV-6 and MneHV-7. This finding supports the existence of two distinct Roseolovirus lineages before the divergence of humans and macaques. Using specific qPCR assays, high levels of MneHV-6 and MneHV-7 DNA were detected in macaque saliva, although the frequency was greater for MneHV-7. A blood screen of 283 macaques revealed 10% MneHV-6 DNA positivity and 25% MneHV-7 positivity, with higher prevalences of MneHV-6 in older females and of MneHV-7 in younger males. Levels of MneHV-6 were increased in animals coinfected with MneHV-7, and both viruses were frequently detected in salivary gland and stomach tissues. Our discovery provides a unique animal model to answer unresolved questions regarding Roseolovirus pathology.
The existence of roseolovirus homologs in non-human primates had been suggested based on serological data (Higashi et al., 1989). Attempts to find HHV-6-like sequences in pig-tailed macaques by HHV-6-specific PCR failed, which led to the assumption that these animals are not commonly infected by a virus related to HHV-6 (Lusso et al., 1994a). Our studies clearly show that pig-tailed macaques are naturally infected with two distinct roseoloviruses closely related to HHV-6 and HHV-7, suggesting that MneHV-6 and MneHV-7 infections in macaques would be an important non-human primate model of roseolovirus infections and pathology. Taken together, our discovery and initial analysis of two novel roseolovirus homologs in macaques offers a unique opportunity to develop relevant animal models using viruses native to the host to answer various unresolved questions surrounding their biology and respective roles as etiological agents in diseases.
The existence of roseolovirus homologs in non-human primates had been suggested based on serological data (Higashi et al., 1989). Attempts to find HHV-6-like sequences in pig-tailed macaques by HHV-6-specific PCR failed, which led to the assumption that these animals are not commonly infected by a virus related to HHV-6 (Lusso et al., 1994a). Our studies clearly show that pig-tailed macaques are naturally infected with two distinct roseoloviruses closely related to HHV-6 and HHV-7, suggesting that MneHV-6 and MneHV-7 infections in macaques would be an important non-human primate model of roseolovirus infections and pathology. Taken together, our discovery and initial analysis of two novel roseolovirus homologs in macaques offers a unique opportunity to develop relevant animal models using viruses native to the host to answer various unresolved questions surrounding their biology and respective roles as etiological agents in diseases.
J Virol. 2016 Jul 11;90(15):6657-6674. doi: 10.1128/JVI.00651-16. Print 2016 Aug 1.
Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques.
Abstract
Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases.
IMPORTANCE:
Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease.
If you have Amazon Prime or Kindle Unlimited you can immediately begin reading this book.
If you have Amazon Prime or Kindle Unlimited, you can immediately begin reading The Chronic Fatigue Syndrome Epidemic Cover-up and you will soon understand why the facts about the Chronic Fatigue Syndrome epidemic have been hidden from the public for almost four decades.
This is the book causing heated debates about Chronic Fatigue Syndrome and HHV-6, "The Fifty Shades of AIDS Virus," in laboratories, doctor's offices, and homes all over the world.
In his bestselling book, The Black Swan, Nassim Nicholas Taleb wrote, "I see the risks of a very strange acute virus spreading throughout the planet." This book by Charles Ortleb warns that the virus causing Chronic Fatigue Syndrome is that virus.
This book belongs in the library of anyone who wants to know the disturbing history of the Chronic Fatigue Syndrome epidemic and the deadly virus HHV-6. Why have the CDC and NIH pretended that the communicable disease fraudulently called "Chronic Fatigue Syndrome" is a mystery for over three decades? By the end of this book of inconvenient truths the answer is crystal clear. The shocking news and bold analysis in this page-turner could lead to a revolution in the science and politics of Chronic Fatigue Syndrome, fibromyalgia, AIDS, autism, and many other illnesses. Scientists, doctors, nurses, patients, journalists, politicians, and historians must begin their journey to a full understanding of the Chronic Fatigue Syndrome epidemic with this book.
As the publisher and editor-in-chief of a small newspaper in New York, Charles Ortleb was the first journalist to devote a publication to uncovering the truth about Chronic Fatigue Syndrome. He assigned Neenyah Ostrom the duty of following every twist and turn of the Chronic Fatigue Syndrome story. No newspaper in the world did more to warn the world about the virus which seems to be triggering Chronic Fatigue Syndrome and many other immunological disorders. Chronic Fatigue Syndrome and AIDS are just the tip of the HHV-6 iceberg.
This provocative book will end the injustice of the silent treatment Neenyah Ostrom's reporting has been getting from the media and The Chronic Fatigue Syndrome community. Ostrom blew the lid off one of the biggest medical secrets of our time: the link between the Chronic Fatigue Syndrome epidemic and AIDS.
Ostrom interviewed most of the major researchers in the field, as well as countless patients and government scientists. She uncovered so many similarities between Chronic Fatigue Syndrome and AIDS that she came to the conclusion that they are part of the same epidemic, and she argued that until their connection is admitted by top government researchers, there is little hope of making real progress in the fight against Chronic Fatigue Syndrome.
Charles Ortleb's book captures all the challenges and excitement of running a small newspaper that was publishing a brilliant journalist who essentially was the Woodward and Bernstein of the Chronic Fatigue Syndrome epidemic. In Rolling Stone, David Black said Ortleb's newspaper deserved a Pulitzer Prize. Randy Shilts praised Ortleb's newspaper in And the Band Played On.
This book belongs in the library of anyone who wants to know the disturbing history of the Chronic Fatigue Syndrome epidemic and the deadly virus HHV-6. Why have the CDC and NIH pretended that the communicable disease fraudulently called "Chronic Fatigue Syndrome" is a mystery for over three decades? By the end of this book of inconvenient truths the answer is crystal clear. The shocking news and bold analysis in this page-turner could lead to a revolution in the science and politics of Chronic Fatigue Syndrome, fibromyalgia, AIDS, autism, and many other illnesses. Scientists, doctors, nurses, patients, journalists, politicians, and historians must begin their journey to a full understanding of the Chronic Fatigue Syndrome epidemic with this book.
As the publisher and editor-in-chief of a small newspaper in New York, Charles Ortleb was the first journalist to devote a publication to uncovering the truth about Chronic Fatigue Syndrome. He assigned Neenyah Ostrom the duty of following every twist and turn of the Chronic Fatigue Syndrome story. No newspaper in the world did more to warn the world about the virus which seems to be triggering Chronic Fatigue Syndrome and many other immunological disorders. Chronic Fatigue Syndrome and AIDS are just the tip of the HHV-6 iceberg.
This provocative book will end the injustice of the silent treatment Neenyah Ostrom's reporting has been getting from the media and The Chronic Fatigue Syndrome community. Ostrom blew the lid off one of the biggest medical secrets of our time: the link between the Chronic Fatigue Syndrome epidemic and AIDS.
Ostrom interviewed most of the major researchers in the field, as well as countless patients and government scientists. She uncovered so many similarities between Chronic Fatigue Syndrome and AIDS that she came to the conclusion that they are part of the same epidemic, and she argued that until their connection is admitted by top government researchers, there is little hope of making real progress in the fight against Chronic Fatigue Syndrome.
Charles Ortleb's book captures all the challenges and excitement of running a small newspaper that was publishing a brilliant journalist who essentially was the Woodward and Bernstein of the Chronic Fatigue Syndrome epidemic. In Rolling Stone, David Black said Ortleb's newspaper deserved a Pulitzer Prize. Randy Shilts praised Ortleb's newspaper in And the Band Played On.
This book continues the work Ortleb has been doing to raise awareness about HHV-6 and Chronic Fatigue Syndrome at his website HHV-6 University. Fewer and fewer people now pretend that HHV-6 is harmless. Thanks to Ortleb's efforts, more and more people are abandoning HHV-6 denialism and admitting the virus is at the center of a public health disaster.
Hillary Johnson, the author of Osler's Web, called it "A rollicking, fascinating and important memoir."
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Purchase the book in the United Kingdom
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