Molecular and Cellular Biology of Viruses

Book Preface

I teach undergraduate students, most of whom are biology, molecular biology, biochemistry, or neuroscience majors. Most undergraduate virology textbooks do not have enough molecular and cellular content for my virology elective. In contrast, most virology textbooks with substantial molecular and cellular content are written for more advanced audiences. There is a singular book from the 1990s that fits this niche, namely The Biology of Viruses by Dr. Bruce A Voyles. But by 2017, it was time for a book of similar scope and focus but incorporating contemporary research.

The book is organized according to the stages of a virus replication cycle, with a few additional chapters to take into account themes in molecular and cellular virology that are especially interesting to undergraduates. These include immunology as it pertains to viral infections and medical applications of molecular and cellular virology. In our age of rising antibiotic resistance and a renaissance in phage research spurred by CRISPR-Cas and other biotechnological innovations, I decided that it would be best to keep the phages front and center even though other authors may have relegated them to an appendix or online materials.

The book is intended to give faculty choices about customizing the assigned reading. For example, faculty whose course goals emphasize molecular biology may want to use all the content about the gene expression and genome replications strategies. In contrast, faculty whose course goals emphasize cell biology may want to use only the simplest model viruses in those chapters so that they can instead assign more content about autophagy, signal transduction, apoptosis, and the cell cycle.

I have not made any attempt to be comprehensive; such a book would have defeated the purpose of its utility for a typical undergraduate course. Instead, I have focused on a few models to give undergraduate readers a taste of the diversity of virology and to lay down examples for comparison. Throughout this book I have favored HIV as an example because its molecular biology has been worked out in intensive detail, using experimental procedures that are understandable by current undergraduates. I also chose to write so much about HIV in order to encourage LGBTQ students and students from the global south to identify with molecular biology. When HIV was not a good choice, I selected models that most interest my students. Throughout, I wrote about ideas derived from contemporary research findings in order to inspire students to love the creation of new knowledge.

I hope that faculty and students will enjoy using this book, and I look forward to hearing from readers.

In this book, you will learn how miniscule viruses enter, take over, and kill our cells. A molecular understanding of these processes provides insights into how both viruses and their host cells function at a molecular level. It is an exciting time to study viruses because of the breadth and depth of techniques available to investigate them, and the increasing number of known viruses and viral genome sequences (including those for viruses that have never been cultivated in the laboratory). In addition, there are many practical applications of virology. For example, basic research on the molecular biology of the human immunodeficiency virus (HIV) ultimately led to the first treatments that moved HIV infection away from being a death sentence to a chronic, controllable illness (Figure 1.1). Many applications such as these attract people to the field of virology.

In this chapter, we examine the origins of virology in order to explain how molecular and cellular virology fit into the broader discipline of virology. Molecular biology is fundamentally concerned with how macromolecules, especially proteins and nucleic acids, function to control the structure and behavior of cells. By extension, molecular and cellular virology studies focus particularly on the interactions among viral proteins, viral nucleic acids, cellular proteins, cellular nucleic acids, and cellular organelles. In Technique Box 1.1, we will see that some of the consequences of viral infection can be observed with a light microscope. After, we consider the characteristics shared by all viruses (Section 1.5). We will then discuss viral diversity (Section 1.6), especially with respect to their genomes and the mechanisms by which they synthesize mRNA (Section 1.7). We will also explain, in Section 1.7, how diverse viruses have been named and classified. We will encounter the general method of propagating viruses in a laboratory setting in Section 1.8. The chapter continues with a consideration of the abundance of viral sequences in the human genome (Section 1.9); indeed, DNA of viral origin is found in almost every known cellular genome, where it contributes to the evolution of organisms, including humans. The chapter concludes with a consideration of how sequences of viral nucleic acids and proteins can be used to generate hypotheses about the evolution, structure, and function of viruses and their component parts.

Our goal in this chapter is to prepare you for the rest of the book. Chapter 2 explains how we will divide the virus replication cycle into several parts. Chapters 3 through 11 will address each of these parts of the cycle in turn, with Chapters 5 through 10 focused on the different Baltimore classes of viruses and how they express and replicate their genomes. In Chapter 12, we will learn how viruses generally interact with host processes such as translation and apoptosis, and in Chapter 13, we will see how viruses can cause integrated and persistent infections that can last for the entire life span of their hosts. In Chapters 14 and 15 we will examine how hosts fight back against viral infections. Chapter 16 is about clinical applications of virology, such as vaccines, gene therapy, and antiviral drugs. Chapter 17 concludes with a discussion of the diversity and evolution of viruses.