Enteroviry
Vaccine associated paralytic poliomyelitis (VAPP)
- In vaccine recipients
Disease caused by circulating vaccine-derived polioviruses (cVDPVs) in contacts
Enteroviruses (EVs) and CNS
- Group of single, positive-stranded RNA viruses
- Of the Picornaviridae family include
- Poliovirus,
- Coxsackievirus,
- Echovirus
- Enterovirus
- EV-A71 and EV-D68 recent large epidemics across the Asia-Pacific and North American region
- Huang and Shih, 2015; Anastasina et al., 2017
- EVs commonly cause asymptomatic infection
- Sometimes they are associated with severe diseases, including neurological complications
- EVs have a high tropism for the central nervous system (CNS)
- Poliomyelitis,
- Aseptic meningitis,
- Encephalitis
- Non-polio flaccid paralysis, particularly in infants and children (Rhoades et al., 2011; Huang and Shih, 2015)
- Since the successful campaign of the poliovirus vaccination
- Neurological diseases caused by non-polio EVs have been increasingly reported
- Acute flaccid paralysis frequently observed among patients with
- EV-A71
- Echovirus
- Coxsackievirus infection (Suresh et al., 2018)
- EV-D68 outbreaks - strong relationship between EV-D68 infection and increased incidence of acute flaccid myelitis
- (Greninger et al., 2015; Messacar et al., 2016)
- www.ncbi.nlm.nih.gov/pmc/articles/PMC5857577/
- Majority of the EVs are transmitted through the fecal-oral route
- Replicate in the gastrointestinal tract
- EVs (e.g., EV-D68) can cause respiratory infection
- Spread via respiratory secretion
- Can invade the CNS from these primary infection sites
- Retrograde axonal transport + trans-synaptic spread (Gromeier and Wimmer, 1998; Chen et al., 2007)
- Blood-brain barrier (BBB) penetration—during viremia (Yang et al., 1997)
- Via transferrin receptor 1-mediated direct transmission (Mizutani et al., 2016)
- “Trojan-horse” invasion—EVs through virus-infected immune cells
- Macrophage/monocytes, dendritic cells, lymphocytes and nesting+ myeloid cells
- Poliovirus infects and replicates in motor neurons within the anterior horns of the spinal cord
- Leading to poliomyelitis (Nagata et al., 2004)
- Motor neurons in the spinal cord and brainstem are also highly susceptible to EV-71 (Ong and Wong, 2015; Too et al., 2016)
- EV-D68 isolates from the 2014 outbreak develop limb paralysis
- Closely resembling human acute flaccid myelitis
- Infection of motor neurons in the anterior horns of spinal cord (Hixon et al., 2017)
- Neuronal cells, especially motor neurons, astrocytes and oligodendrocytes
- Are also permissive to poliovirus (Couderc et al., 2002)
- EV-A71 (Tung et al., 2010)
- Coxsackievirus B3 (CVB3; Zhang et al., 2013)
- CVB3 and EV-A71 preferentially target neural progenitor cells
- Compared with differentiated neuronal cells (Feuer et al., 2005; Tsueng et al., 2011; Huang et al., 2014).
- EVs, such as poliovirus (Julien et al., 1999), EV-A71 (Han et al., 2010), and coxsackievirus (Feuer et al., 2009)
- Can persist in various tissues, including the CNS
- Glial cells and neuronal progenitor cells
- Sites of CVB3 persistence (Feuer et al., 2009; Zhang et al., 2013)
- Latent EVs might be reactivated years later
- Spontaneously or in response to exogenous stimulations, such as local trauma (Andréoletti et al., 2000; Feuer et al., 2002)
- EV persistence in cardiomyocytes and pancreatic cells
- Associated with chronic clinical conditions
- Dilated cardiomyopathy
- Type 1 diabetes, mainly through continuous inflammatory responses (Chapman and Kim, 2008; Oikarinen et al., 2012)
- Polio survivors decades after the recovery from the acute paralytic poliomyelitis
- Can develop post-poliomyelitis syndrome
- New and progressive muscular weakness
- Defective viral particles in the cerebrospinal fluid of some patients (Dalakas, 1995)
- Neonatal CVB3 infection
- Can have a chronic impact on neurogenesis and CNS development
- Potential link between early subclinical infections and late neurological sequelae (Ruller et al., 2012)
Enteroviruses (EVs) and CNS
- Group of single, positive-stranded RNA viruses
- Of the Picornaviridae family include
- Poliovirus,
- Coxsackievirus,
- Echovirus
- Enterovirus
- EV-A71 and EV-D68 recent large epidemics across the Asia-Pacific and North American region
- Huang and Shih, 2015; Anastasina et al., 2017
- EVs commonly cause asymptomatic infection
- Sometimes they are associated with severe diseases, including neurological complications
- EVs have a high tropism for the central nervous system (CNS)
- Poliomyelitis,
- Aseptic meningitis,
- Encephalitis
- Non-polio flaccid paralysis, particularly in infants and children (Rhoades et al., 2011; Huang and Shih, 2015)
- Since the successful campaign of the poliovirus vaccination
- Neurological diseases caused by non-polio EVs have been increasingly reported
- Acute flaccid paralysis frequently observed among patients with
- EV-A71
- Echovirus
- Coxsackievirus infection (Suresh et al., 2018)
- EV-D68 outbreaks - strong relationship between EV-D68 infection and increased incidence of acute flaccid myelitis
- (Greninger et al., 2015; Messacar et al., 2016)
- www.ncbi.nlm.nih.gov/pmc/articles/PMC5857577/
- Majority of the EVs are transmitted through the fecal-oral route
- Replicate in the gastrointestinal tract
- EVs (e.g., EV-D68) can cause respiratory infection
- Spread via respiratory secretion
- Can invade the CNS from these primary infection sites
- Retrograde axonal transport + trans-synaptic spread (Gromeier and Wimmer, 1998; Chen et al., 2007)
- Blood-brain barrier (BBB) penetration—during viremia (Yang et al., 1997)
- Via transferrin receptor 1-mediated direct transmission (Mizutani et al., 2016)
- “Trojan-horse” invasion—EVs through virus-infected immune cells
- Macrophage/monocytes, dendritic cells, lymphocytes and nesting+ myeloid cells
- Poliovirus infects and replicates in motor neurons within the anterior horns of the spinal cord
- Leading to poliomyelitis (Nagata et al., 2004)
- Motor neurons in the spinal cord and brainstem are also highly susceptible to EV-71 (Ong and Wong, 2015; Too et al., 2016)
- EV-D68 isolates from the 2014 outbreak develop limb paralysis
- Closely resembling human acute flaccid myelitis
- Infection of motor neurons in the anterior horns of spinal cord (Hixon et al., 2017)
- Neuronal cells, especially motor neurons, astrocytes and oligodendrocytes
- Are also permissive to poliovirus (Couderc et al., 2002)
- EV-A71 (Tung et al., 2010)
- Coxsackievirus B3 (CVB3; Zhang et al., 2013)
- CVB3 and EV-A71 preferentially target neural progenitor cells
- Compared with differentiated neuronal cells (Feuer et al., 2005; Tsueng et al., 2011; Huang et al., 2014).
- EVs, such as poliovirus (Julien et al., 1999), EV-A71 (Han et al., 2010), and coxsackievirus (Feuer et al., 2009)
- Can persist in various tissues, including the CNS
- Glial cells and neuronal progenitor cells
- Sites of CVB3 persistence (Feuer et al., 2009; Zhang et al., 2013)
- Latent EVs might be reactivated years later
- Spontaneously or in response to exogenous stimulations, such as local trauma (Andréoletti et al., 2000; Feuer et al., 2002)
- EV persistence in cardiomyocytes and pancreatic cells
- Associated with chronic clinical conditions
- Dilated cardiomyopathy
- Type 1 diabetes, mainly through continuous inflammatory responses (Chapman and Kim, 2008; Oikarinen et al., 2012)
- Polio survivors decades after the recovery from the acute paralytic poliomyelitis
- Can develop post-poliomyelitis syndrome
- New and progressive muscular weakness
- Defective viral particles in the cerebrospinal fluid of some patients (Dalakas, 1995)
- Neonatal CVB3 infection
- Can have a chronic impact on neurogenesis and CNS development
- Potential link between early subclinical infections and late neurological sequelae (Ruller et al., 2012)
