Vaccines for Latent Viral Infections

by

Liljana Stevceva

DOI: 10.2174/97816810813281150101
eISBN: 978-1-68108-132-8, 2015
ISBN: 978-1-68108-133-5



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Many viruses are known to persist in their host’s cells in a latent state without exhibiting virulence or symptoms of infection, hence...[view complete introduction]
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Table of Contents

Foreword

- Pp. i
Joseph Silva
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Preface

- Pp. iii
Liljana Stevceva
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List of Contributors

- Pp. v
Liljana Stevceva
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Latent Viral Infections in Humans

- Pp. 3-8 (6)
Liljana Stevceva
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Characteristics of Viruses that Induce Latent Infections

- Pp. 9-23 (15)
Bhargavi Patham, Nelly Estrada and Sandesh Subramanya
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Herpes Simplex Virus Infections and Vaccine Advances

- Pp. 25-36 (12)
Tu Thanh Mai and Liljana Stevceva
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Immune Responses to CMV and Vaccine Development

- Pp. 37-59 (23)
Masha Fridkis-Hareli
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Varicella-Zoster Virus Infections and Vaccine Advances

- Pp. 61-70 (10)
Kallie Appleton, Ghaith Al Eyd and Liljana Stevceva
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Epstein-Barr Virus Infections and Vaccine Advances

- Pp. 71-97 (27)
Risaku Fukumoto
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Human Immunodeficiency Virus

- Pp. 99-115 (17)
Liljana Stevceva
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Vaccines Against Latent Viral Infections: Pathway Forward

- Pp. 117-131 (15)
Liljana Stevceva
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Subject Index

- Pp. 133-137 (5)
Liljana Stevceva
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Foreword

Yin – Yang (Taoistic symbol for Representation of Perfect Balance)

Definition: Latency (Present but not visible or apparent).

This book updates readers in the relatively misunderstood field of viral latency. Their major focus is the status of vaccines in the prevention and treatment of a broad array of viruses capable of persisting via latency. It is important to differentiate between a virus in a state of latency (i.e. dormancy [often the lysogenic phase of a virus life cycle]) from viruses which chronically infect cells. Dormancy is the recognition that following the initial acute infection, proliferation of the virus is terminated for a variable period (often the life span of the host). When it does “awake”, the lytic part of the cycle is activated causing replication and shedding, and thus reinfection.

The Chinese symbol above can be applied to the two types of viral latency – proviral versus episomal viral genetic material. Viral RNA or DNA hibernates in either the cytoplasm or nucleus as a foreign “immigrant”. This state is vulnerable to the host’s gene degradation and/or ribosomes. The fascinating aspect of how episomal viruses avoid the intracellular immune attack is that they remain outside the nucleus, which greatly reduces triggering an interferon attack via the Nuclear Domain 10. But the flip side of this “yin” is that these viruses are still subjected to degradation by cytoplasmic enzymes.

The other side of latency (the yang) is to the proviral universe of viral DNA integrated into the nuclear “stuff” of its host. These viruses enjoy a protected and cozy life intertwined within the host DNA and can only be eliminated by killing the entire cell. They require packaging proteins for entering the nuclear haven, which compromises latency over time.

The authors address the respective mechanisms of maintaining latency for both types of viral states, and the influence of the envelope glycoproteins for sustaining latency.

These latent viruses have different relationships in the host which range from symbiosis to outright parasitism, leading to a variety of clinical consequences. The authors describe the effectiveness of vaccines in terminating or ameliorating these infections that affect most life forms. Only partial explanations are available to what do these integrated latent virus contribute to the host as large areas of RNA/DNA have integrated viral sequences. The yin is they are present and tolerated – the yang has led to many speculations that they influence immunity, anthropomorphic textures, organogenesis, personality, genetics of the host, behavior etc. Are they overall beneficial (the yin) or deleterious (the yang). If the latter, why is the persistence so long? More effective vaccines against these latent viruses may eventually provide insights to the ultimate consequences of viral latency by demonstrating total prevention against latency or even eliminating viral latency form the host.

Joseph Silva
Founding Dean
Vice President for Medical Affairs
Professor of Internal Medicine and Infectious Diseases
California Northstate University College of Medicine
Dean Emeritus, UC Davis School of Medicine
USA


Preface

I now believe that the first buds about writing this book germinated fifteen years ago when I started seriously looking into the structure and function of the HIV gp120 glycoprotein. I became aware of the unique immunomodulating properties of sulfated polysaccharides during my PhD studies at the Australian National University. As soon as my research shifted to HIV and HIV vaccine development, the similarity of the way the envelope of the HIV was constructed to these compounds attracted my attention and I began wondering how much of the immunomodulating properties do the envelope possess and how the virus uses it. Significant scientific effort was devoted in the past 20 years to dissecting the structure of the HIV envelope glycoproteins but it still appears that our thinking about the HIV envelope did not take into account sufficiently its function and usefulness for the virus. Bearing in mind that all of the known HIV vaccine candidates had envelope component in them, this might have significantly affected their efficacy. As we are now embarking into a new era in HIV vaccine development, perhaps it is pertinent to revisit the basic immunomodulatory role of the HIV glycoproteins and mechanisms of viral escape as they relate to HIV vaccines.

My research interests recently widened to include other viruses that are capable of evading the immune response and establishing a state of latency. As I began embarking deeper into researching these viruses, it soon became very obvious to me that the envelopes of all of them contain similar structures that allow them to modulate the immune response. It also became apparent that any past or present vaccine development effort related to these viruses is directed towards developing vaccine that will prevent clinical manifestation i.e. disease (or what we are able to detect of it) but that there was never an effort to prevent establishment of dormant viral state. Perhaps the reason for this was that until recently, the presence of latent viruses was largely underestimated and that it was widely believed not to cause any harm to the human body as long as the immune system is intact. Novel findings from the human genome sequencing as well as emerging findings on the potential role of CMV infection in immunosenescence are however revealing that this might not be the case. It is time to have a second look at the viruses that are capable of causing latent infection and to shift the scientific taught towards preventing establishment of latency.

Liljana Stevceva,
University of Texas Rio Grande Valley
School of Medicine
2102 Treasure Hills Blvd.,
Harlingen TX
USA

DEDICATION:

I would like to dedicate this book to my parents Galaba and Risto Vitanovi who taught me that honesty, hard work and perseverance are the only way to live our lives and to my children Ilija and Risto Stevcev that always inspire me to persist and move forward.

Mom when you were studying late at night after long hours of work and taking care of us, you thought that we were sleeping but I NOTICED. Dad, all the times when you were strict but just to a student, I NOTICED; every time when you put additional effort to understand and help a student, I NOTICED, and every time you turned away any attempt of bribery even at times difficult for our family, I NOTICED. Thank you for teaching me about important things in life. I could not have asked for better parents.

The only way that we will not achieve what we strive for is if we stop trying.

List of Contributors

Editor(s):
Liljana Stevceva




Contributor(s):
Barghavi Patham
Baylor College of Medicine Endocrinology
1504 Taub Loop
Houston
TX, 77030
USA


Ghaith Al Eyd
California Northstate University College of Medicine
9700 West Taron Drive
Elk Grove
CA
USA


Kallie Rebekah Appleton
The Paul Foster School of Medicine
TexasTech, 3068 Hayden Road
Columbus
Ohio, 43235
USA


Liljana Stevceva
University of Texas Rio Grande Valley School of Medicine
2102 Treasure Hills Blvd.
Harlingen
TX
USA


Masha Fridkis-Hareli
ATR LLC
Sudbury
MA, 01776
USA


Nelly Estrada
The Paul Foster School of Medicine
TexasTech, 5001 El Paso Drive
El Paso
TX, 79905
USA


Risaku Fukumoto
Scientific Research Department
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences
USA


Sandesh Subramanya
Bioo Scientific Corp.
7050 Burleson Rd.
Austin
TX, 78744
USA


Tu Thanh Mai
The Paul Foster School of Medicine
TexasTech, 5001 El Paso Drive
El Paso
TX, 79905
USA
/
2401 S 31ST ST
Temple
TX, 76508
USA




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