Evolution of Virology: Science History through Milestones and Technological Advancements.

The history of virology, which is marked by transformative breakthroughs, spans microbiology, biochemistry, genetics, and molecular biology. From the development of Jenner's smallpox vaccine in 1796 to 20th-century innovations such as ultrafiltration and electron microscopy, the field of virology has undergone significant development. In 1898, Beijerinck laid the conceptual foundation for virology, marking a pivotal moment in the evolution of the discipline. Advancements in influenza A virus research in 1933 by Richard Shope furthered our understanding of respiratory pathogens. Additionally, in 1935, Stanley's determination of viruses as solid particles provided substantial progress in the field of virology. Key milestones include elucidation of reverse transcriptase by Baltimore and Temin in 1970, late 20th-century revelations linking viruses and cancer, and the discovery of HIV by Sinoussi, Montagnier, and Gallo in 1983, which has since shaped AIDS research. In the 21st century, breakthroughs such as gene technology, mRNA vaccines, and phage display tools were achieved in virology, demonstrating its potential for integration with molecular biology. The achievements of COVID-19 vaccines highlight the adaptability of virology to global health.

Bo Zhong: Captive by the viral immune escape.

Bo Zhong studies the regulation of the antiviral innate immunity, inflammation, and tumorigenesis by the protein ubiquitination system.

Retroviral Antisense Transcripts and Genes: 33 Years after First Predicted, a Silent Retroviral Revolution?

Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been especially true in the field of virology, where the discovery of a "contagium vivum fluidum", or infectious fluid remaining after excluding bacteria by filtration, was initially ignored because it did not coincide with the established view of microorganisms. Subsequent studies on such infectious agents, eventually termed "viruses", were met with skepticism. However, after an abundance of proof accumulated, viruses were eventually acknowledged as defined microbiological entities. Next, the proposed role of viruses in oncogenesis in animals was disputed, as was the unique mechanism of genome replication by reverse transcription of RNA by the retroviruses. This same pattern of skepticism holds true for the prediction of the existence of retroviral "antisense" transcripts and genes. From the time of their discovery, it was thought that retroviruses encoded proteins on only one strand of proviral DNA. However, in 1988, it was predicted that human immunodeficiency virus type 1 (HIV-1), and other retroviruses, express an antisense protein encoded on the DNA strand opposite that encoding the known viral proteins. Confirmation came quickly with the characterization of the antisense protein, HBZ, of the human T-cell leukemia virus type 1 (HTLV-1), and the finding that both the protein and its antisense mRNA transcript play key roles in viral replication and pathogenesis. However, acceptance of the existence, and potential importance, of a corresponding antisense transcript and protein (ASP) in HIV-1 infection and pathogenesis has lagged, despite gradually accumulating theoretical and experimental evidence. The most striking theoretical evidence is the finding that asp is highly conserved in group M viruses and correlates exclusively with subtypes, or clades, responsible for the AIDS pandemic. This review outlines the history of the major shifts in thought pertaining to the nature and characteristics of viruses, and in particular retroviruses, and details the development of the hypothesis that retroviral antisense transcripts and genes exist. We conclude that there is a need to accelerate studies on ASP, and its transcript(s), with the view that both may be important, and overlooked, targets in anti-HIV therapeutic and vaccine strategies.

A History of Cancer Research: Tumor Viruses.

Early studies of transmissible tumors in chickens provided evidence that viruses such as avian leukosis virus (ALV) and Rous sarcoma virus (RSV) can cause cancer in these animals. Doubts about the relevance to human tumors and failures to replicate some early work meant the field of tumor virology followed a bumpy course. Nevertheless, viruses that can cause cancers in rodents and humans were ultimately identified, and several Nobel prizes were awarded for work in this area. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the early history of tumor virus research, from some of the early false starts and debates, to discovery of reverse transcriptase, and identification of human papilloma virus (HPV) as the major cause of cervical cancer.

Mark Prichard: Scholar, family man and friend.

Mark Prichard, professor of pediatrics at the University of Alabama at Birmingham, an expert in antiviral therapy and an editor for Antiviral Research, died in June, 2019 after a long battle with cancer. He was widely known and respected in the research community for his work on the development of new treatments for DNA virus infections. This article pays tribute to Mark as a scholar, family man and friend.

Membrane-Containing Icosahedral Bacteriophage PRD1: The Dawn of Viral Lineages.

Membrane-containing enterobacterial phage PRD1 was isolated from sewage more than 40 years ago. At that time none would have expected the impact that unravelling its biology would have on modern virology and on the way we understand virus assembly, evolution and classification today. PRD1 structural analyses have provided a framework for understanding some aspects of virus evolution-introducing the concept of "viral lineages"-where the three-dimensional structures of virus capsids represent the fingerprint for evolutionary relationship which cannot be traced from the sequence data. In this review we summarise those findings that have led to the notion of viral lineages and the multidisciplinary efforts made in elucidating PRD1 life cycle. These studies have rendered PRD1 a model system not only for the family Tectiviridae to which it belongs, but more generally to complex DNA viruses enclosing a membrane vesicle beneath the capsid shell.

Encounters with adenovirus.

In this paper I describe aspects of work on the human adenoviruses in which my laboratory has participated. It consists of two sections-one historic dealing with work performed in the previous century, and one dealing with the application of 'omics' technologies to understand how adenovirus-infected cells become reprogrammed to benefit virus multiplication.

On the historical significance of Beijerinck and his contagium vivum fluidum for modern virology.

This paper considers the foundational role of the contagium vivum fluidum-first proposed by the Dutch microbiologist Martinus Beijerinck in 1898-in the history of virology, particularly in shaping the modern virus concept, defined in the 1950s. Investigating the cause of mosaic disease of tobacco, previously shown to be an invisible and filterable entity, Beijerinck concluded that it was neither particulate like the bacteria implicated in certain infectious diseases, nor soluble like the toxins and enzymes responsible for symptoms in others. He offered a completely new explanation, proposing that the agent was a "living infectious fluid" whose reproduction was intimately linked to that of its host cell. Difficult to test at the time, the contagium vivum fluidum languished in obscurity for more than three decades. Subsequent advances in technologies prompted virus researchers of the 1930s and 1940s-the first to separate themselves from bacteriologists-to revive the idea. They found in it both the seeds for their emerging virus concept and a way to bring hitherto opposing thought styles about the nature of viruses and life together in consensus. Thus, they resurrected Beijerinck as the founding father, and contagium vivum fluidum as the core concept of their discipline.

Finding, Conducting, and Nurturing Science: A Virologist's Memoir.

My laboratory investigations have been driven by an abiding interest in understanding the consequences of genetic rearrangement in evolution and disease, and in using viruses to elucidate fundamental mechanisms in biology. Starting with bacteriophages and moving to the retroviruses, my use of the tools of genetics, molecular biology, biochemistry, and biophysics has spanned more than half a century-from the time when DNA structure was just discovered to the present day of big data and epigenetics. Both riding and contributing to the successive waves of technology, my laboratory has elucidated fundamental mechanisms in DNA replication, repair, and recombination. We have made substantial contributions in the area of retroviral oncogenesis, delineated mechanisms that control retroviral gene expression, and elucidated critical details of the structure and function of the retroviral enzymes-reverse transcriptase, protease, and integrase-and have had the satisfaction of knowing that the fundamental knowledge gained from these studies contributed important groundwork for the eventual development of antiviral drugs to treat AIDS. While pursuing laboratory research as a principal investigator, I have also been a science administrator-moving from laboratory head to department chair and, finally, to institute director. In addition, I have undertaken a number of community service, science-related "extracurricular" activities during this time. Filling all of these roles, while being a wife and mother, has required family love and support, creative management, and, above all, personal flexibility-with not too much long-term planning. I hope that this description of my journey, with various roles, obstacles, and successes, will be both interesting and informative, especially to young female scientists.

125 years of virology and ascentof biotechnologies based on viral expression.

The study of viruses lasts for more than a century since their discovery in 1892. In recent decades, viruses are also being actively exploited as a biotechnological tool. Plant-virus-driven transient expression of heterologous proteins is an actively developing production platform; it is the basis of several industrial processes that are currently being used for the production of multiple recombinant proteins. Viral vectors have also become useful tools for research. Viral vectors delivered by Agrobacterium (magnifection) provide for high pro-tein yield, rapid scale up and fast manufacturing. In this review, we explore modern approaches for bio technological production of recombinant proteins in plants using viral vectors.

45 years after the discovery of human polyomaviruses BK and JC: Time to speed up the understanding of associated diseases and treatment approaches.

Nearly 45 years after the discovery of the first two human polyomaviruses BK and JC, their life-long persistence and mechanisms of pathogenesis remain poorly understood and efficient antiviral treatments are severely lacking. In this review, we sought to provide an update on recent advances in understanding the life cycle of these two viruses, particularly focusing on their interaction with the host immune system and pathogenesis. We have also discussed novel treatment approaches and highlighted areas of future research.

A Tribute to Professor Steven L. Wechsler (1948-2016): The Man and the Scientist.

Professor Steven L. Wechsler, a world-renowned eye researcher and virologist, passed away unexpectedly on June 12, 2016 at the age of 68. Many scientists came to know Professor Wechsler as a gifted researcher in the field of ocular Herpes Simplex Virus (HSV-1) latency, reactivation, and pathogenesis. Professor Wechsler published over 150 peer-reviewed scientific papers during his career, pushing forward the frontiers of his field eye research. His colleagues would say, 'Steve literally wrote the book on herpes latency and reactivation.' He was the first to show that the HSV-1 latency-associated transcript (LAT) is essential for the HSV-1 high spontaneous reactivation phenotype and that LAT has anti-apoptosis activity. This discovery of LAT's anti-apoptosis activity, which is a key factor in how the LAT gene enhances reactivation, was published in Science in 2000 and created a new paradigm that greatly increased understanding of HSV-1 latency and reactivation. In collaboration with Professor Lbachir BenMohamed, an immunologist, they later demonstrated that LAT also acts as an immune evasion gene. He was a caring scientist who truly enjoyed working and sharing his experience and expertise with young researchers. He will be remembered as a significant pillar within scientific and ocular herpes research communities worldwide. Professor Wechsler's dedication to science, his compassionate character, and wonderful sense of humor were exemplary. We, who were his friends and colleagues, will mourn his passing deeply.