The totality of HBoV1 sequences collected worldwide by multiple groups show very low protein and nucleotide sequence diversity (Table 2 and Figure 4A ) [35, 36] . In contrast, this single study found substantial diversity among HBoV2 and HBoV3, a fourth species (HBoV4), and extensive viral recombination (Figures 3, 4B, and 4C ). Assuming comparable rates of evolution, the genetically homogeneous and largely respiratory HBoV1, therefore, appears to be the more recently evolved species relative to the more diverse HBoV2, 3, and 4 found predominantly in feces. We propose that HBoV1 evolved from an enteric bocavirus ancestor that acquired, through mutation and/or recombination, enhanced respiratory tract tropism. Single-stranded DNA parvoviruses have been shown to have a mutation rate approaching that of RNA viruses, and recombination among animal parvoviruses has also been reported [45] [46] [47] . Parvoviruses have also demonstrated the capacity to rapidly expand their host species tropism, resulting in a recent pandemic in dogs [42, 48, 49] . A recent study showed that HBoV1 could replicate in differentiated human airway epithelial cells [41] . Whether HBoV2, 3, and 4 show an in vitro tropism and in vivo distribution that is more biased towards digestive track cells will require further study. The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection In order to establish an infection, viruses need to either suppress or escape from host immune defense systems. Recent immunological research has focused on innate immunity as the first line of host defense, especially pattern recognition molecules such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs). Various microbial components are recognized by their vague and common molecular shapes so-called, pathogen-associated molecular patterns (PAMPs). PAMPs induce inflammatory reactions mediated by the activation of the transcription factor, NF-κB, and by interferons, which lead to an antiviral immune response. Viruses have the capacity to suppress or escape from this pattern recognition molecule-mediated antimicrobial response in various ways. In this paper, we review the various strategies used by viruses to modulate the pattern recognition molecule-mediated innate immune response. The host immune system recognizes and eliminates invading pathogenic microorganisms such as viruses, bacteria, and fungi. The first line of defense in mammals is the innate immune system. Recently, the mechanisms by which the innate immune system recognizes pathogen have been extensively studied. Pattern recognition molecules/pathogen recognition receptors (PRRs) are classified into three families: Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and nucleotide binding-oligomerization domain (NOD)-like receptors (NLRs) [1, 2] . Ten TLRs (TLR1 to 10) have been identified in humans. The RLR family contains retinoic acid-inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) [3] . The NLR receptor family contains NOD1, NOD2, NLRP3, NLRPC5, NLRP1, NAIP, and CIITA [4] . In addition, DNA-dependent activator of interferon regulatory factors (DAI) has been identified as a DNA sensor [5] . Various microbial components are recognized as their vague and common molecular shapes by PRRs. Early responses against virus infection are initiated on recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition molecules, triggering two responses. One is the production of interferons (IFNs) resulting in an antiviral state as part of the innate immune response, and the second is maturation of dendritic cells (DCs) to establish acquired immunity. In order to establish an infection within a host, viruses must escape from and/or suppress the immune system by various strategies. An important strategy used by viruses is modulation of PAMPinduced immune responses.