Natural recombination in alphaherpesviruses: Insights into viral evolution through full genome sequencing and sequence analysis

Abstract

Recombination in alphaherpesviruses was first described more than sixty years ago. Since then, different techniques have been used to detect recombination in natural (field) and experimental settings. Over the last ten years, next-generation sequencing (NGS) technologies and bioinformatic analyses have greatly increased the accuracy of recombination detection, particularly in field settings, thus contributing greatly to the study of natural alphaherpesvirus recombination in both human and veterinary medicine. Such studies have highlighted the important role that natural recombination plays in the evolution of many alphaherpesviruses. These studies have also shown that recombination can be a safety concern for attenuated alphaherpesvirus vaccines, particularly in veterinary medicine where such vaccines are used extensively, but also potentially in human medicine where attenuated varicella zoster virus vaccines are in use. This review focuses on the contributions that NGS and sequence analysis have made over the last ten years to our understanding of recombination in mammalian and avian alphaherpesviruses, with particular focus on attenuated live vaccine use.

Genetic Diversity of Infectious Laryngotracheitis Virus duringIn VivoCoinfection Parallels Viral Replication and Arises from Recombination Hot Spots within the Genome

“…Expanding standard vaccine characterization studies to include examination of a vaccine's capacity to reduce viral replication after subsequent challenge (as measured by viral titers), and potentially viral recombination, would help to further control disease caused by this virus. Similar approaches could be taken for other attenuated live vaccines that are used to control alphaherpesviruses, such as FeHV-1, BoHV-1, and PRV, in veterinary medicine (24,25) and for varicella-zoster virus (VZV) vaccines in human medicine (26), as these viruses all have capacity for recombination (3).…”

“…Recombination between different strains of ILTV has been recognized as a problem for the poultry industry, particularly because natural recombination between attenuated vaccine strains of ILTV has been shown to generate virulent viruses (2). The importance of recombination as a mechanism of viral genome diversification and evolution in ILTV and other alphaherpesviruses is increasingly being recognized (3). Viruses can acquire genetic changes through several mechanisms, including point mutation and recombination, with the latter particularly important in many alphaherpesviruses (4)(5)(6).…”

Evidence of natural interspecific recombinant viruses between bovine alphaherpesviruses 1 and 5

“…The detection of natural recombination in alphaherpesviruses varies from limited or absent in FeHV-1 and equid herpesvirus 1 (EHV-1) (Vaz et al, 2016a;Vaz et al, 2016b) to widespread in HSV-1, EHV-4 and gallid herpesvirus 1 (GaHV-1) Lee et al, 2013;Lee et al, 2012;Szpara et al, 2014;Vaz et al, 2016a) suggesting that the contribution that recombination makes to genomic diversification and evolution in alphaherpesviruses varies across the different virus species (Loncoman et al, 2017).…”

“…Whether viral recombination in general is driven by mechanistic constraints associated with genome structures or is selectively favoured as a means to increase genetic diversity end eliminate deleterious mutations, it is undisputed that recombination can be considered as an essential driving force to increase the occurrence of rare but advantageous mutations within a viral species . Highlighting the importance of recombination during herpesvirus history, sequence analysis has shown strong evidence of past natural homologous recombination events in several species, including human (Loncoman et al, 2017;Norberg et al, 2007Norberg et al, , 2006Norberg et al, , 2004Peters et al, 2006) and animal (Hughes and Rivailler, 2007;Lee et al, 2011Lee et al, , 2015Pagamjav et al, 2005) alphaherpesviruses.…”

Development and application of a TaqMan single nucleotide polymorphism genotyping assay to study infectious laryngotracheitis virus recombination in the natural host

“…More recently, another virulent recombinant virus, class 10 ILTV, has emerged in Australia to become dominant in some poultry producing regions [6]. Recently a review compiling ten years of research has helped to understand the importance of recombination in alphaherpesviruses evolution [7], showing that recombination allows some alphaherpesviruses to persist, evolve, and become more virulent through time [3, 5, 8–12]. As alphaherpesviruses have a DNA polymerase with a highly efficient proofreading activity, these viruses have very low genetic mutation rates [13, 14] and so recombination can be particularly important for herpesvirus genome diversification [3, 15, 16].…”