Viral and Host Strategies for Regulation of Latency and Reactivation in Equid Herpesviruses

Abstract

Nine members of the family Herpesviridae infect equines and two of them (EHV1 and EHV4) are the globally significant pathogens causing respiratory disease, abortion and more rarely paralysis. The ability of equid herpesviruses to establish lifelong latent infection in lymphoid and neural tissues with periodic reactivation and shedding is central to the maintenance of these viruses in horse populations. Over 50% of horses become latently infected after infection with EHV1 and EHV4. During latency, expression of viral genes is highly restricted with expression of few or no viral proteins. The recent scientific advances have provided insight into the mechanism of equine herpesvirus pathogenesis, including latency. The establishment of latent infection is highly coordinated process regulated by interplay of viral, host and environmental factors. In this article, we review how molecular, cellular and viral regulatory mechanisms influence the switch between latent and lytic infections.

Molecular Surveillance of EHV-1 Strains Circulating in France during and after the Major 2009 Outbreak in Normandy Involving Respiratory Infection, Neurological Disorder, and Abortion

“…The virus can be reactivated after environmental stimuli (e.g., stress) or therapeutic treatment (e.g., dexamethasone) and replicate in mucous tissues with subsequent dissemination to other hosts [11]. EHV-1 latency mechanisms are poorly understood, although gene regulation has been shown to play a major role in the process [12].…”

Recent advancements in our understanding of equid gammaherpesvirus infections

“…Herpesviruses can sustain their presence in natural host populations by establishing lifelong latent infections in host lymphoid and neural tissues, periodically reactivating to lytic infections. 23,33 The criteria for latency have been debated but classically encompasses the presence of the viral genome without the presence of the infectious preformed virus. 34 During latency the whole viral genome is retained in infected cells but only restricted sections known as latencyassociated transcripts (LATs) are transcribed enabling the virus to evade the host immune system.…”

“…34 During latency the whole viral genome is retained in infected cells but only restricted sections known as latencyassociated transcripts (LATs) are transcribed enabling the virus to evade the host immune system. 23 This process is coordinated by a combination of viral, host and environmental factors. Members of Alphaherpesvirinae subfamily establish latency in neural tissues, lymphoid tissues and peripheral blood leucocytes, while gammaherpesviruses establish latency in lymphoid tissue and peripheral blood leucocytes.…”

“…96,97 Foals shed higher EHV-2 viral loads than mature horses, with the prevalence and shedding decreasing as antibody levels increase. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]29 Seroconversion has been used to diagnose active infections. 29,70,76,80,98,99 However, studies have suggested that EHV-2 antibody titres vary independently of clinical signs and do not appear to correlate with protective immunity.…”

“…During equine herpesvirus latency, the expression of viral genes is restricted to enable the virus to evade the host immune system. 23 The transcription and translation processes of all gene classes are turned off in infected cells and only latency-associated transcripts are expressed. 23,36 The viral genome is subsequently reactivated leading to the reappearance of infectious virus.…”