The human virome in health and disease

Early studies of the human microbiome were directed at bacteria. However, just as the bacterial microbiota affects human health and disease, viruses have analogous interactions. Thus, the human microbiome should be thought of as having a viral component, which is designated the human virome (Fig. 1 and Table 1). The definition of the human virome is complicated by the complexity of viruses and their life cycles. Viruses may be associated with acute infections that may or may not produce manifestations of disease and in which the presence of the viral etiologic agent is transient. In other cases, viral infections are persistent with prolonged presence of the implicated virus and ongoing replication. Persistent infections may or may not be associated with disease. In addition, some viruses become latent following acute infection. During latency, the viral genome persists, but viral replication does not occur, although transcription of some viral genes may take place. Another component of the virome consists of sequences within the human genome that appear to have resulted from remote incorporation of viral elements into the human genome. Designated as endogenous human retroviruses, these sequences cannot generate infectious viral particles. They occupy approximately 4.8% of the human genome (1). Finally, bacteriophages are viruses that infect the bacteria that make up the human endogenous microbiota. While all of the forms of viral infection described above may legitimately be considered part of the human virome, this chapter will focus on the first three groups: namely, viruses that infect eukaryotic cells and are capable of independent replication. The reason for that focus is that these are the viruses that have been associated to date with human disease and are the targets of diagnostic testing.