MicrobiologyBytes

It was my privilege to work with Phil Minor during my PhD. 25 years later (gulp), Phil looks back and forward to the polio endgame.

The Polio-Eradication programme and issues of the end game. J Gen Virol. Nov 29 2011
Poliovirus causes paralytic poliomyelitis, an ancient disease of humans that became a major public health issue in the 20th century. The primary site of infection is the gut where virus replication is entirely harmless; the two very effective vaccines developed in the 1950s (Oral Polio Vaccine, or OPV and Inactivated Polio Vaccine, or IPV) induce humoral immunity which prevents viraemic spread and disease. The success of vaccination in developing countries and in middle income countries encouraged the World Health Organization to commit itself to an eradication programme which has made great advances. The features of the infection including its largely silent nature and the ability of the live vaccine (OPV) to evolve and change in vaccine recipients and their contacts make eradication particularly challenging. Understanding the pathogenesis and virology of the infections is of major significance as the programme reaches its conclusion.

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Neurotropic viruses, including herpesviruses, rabies virus, and poliovirus, initiate infection in the periphery and can move through peripheral neurons to reach the central nervous system (CNS). Since peripheral neurons can be up to one meter long, inefficient neural transport could dramatically affect pathogenesis of neurotropic viruses. This study uses a novel viral “bar-coding” assay to quantify the efficiency of poliovirus transport from the periphery to the CNS in mice. Only 20% of the poliovirus population successfully moved from the periphery to the CNS. Transport of poliovirus in peripheral neurons was very inefficient, and the innate immune response also limited viral movement. Surprisingly, the neural transport barrier was as strong as the innate immune response barrier. Importantly, by overcoming both the neural transport and innate immune barriers, 80% of the poliovirus population successfully moved from the periphery to the CNS, and mice succumbed to disease three times faster than mice with intact barriers. This study identifies inefficient neural transport as a substantial barrier to viral movement in peripheral neurons, which may limit CNS access for many viruses. Peripheral nervous system barriers may contribute to the low incidence of paralytic poliomyelitis in humans, and may also contribute to inefficient trafficking of other neurotropic viruses.

Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response. 2010 PLoS Pathog 6(3): e1000791. doi:10.1371/journal.ppat.1000791

I started my scientific career working on vaccine-derived polioviruses. We’ve come a long way since those distant days and we’re slowly getting closer to eradicating polio worldwide, but it’s not all over yet:

In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. Subsequently, the Global Polio Eradication Initiative of the World Health Organization (WHO) reduced the global incidence of polio associated with wild polioviruses (WPVs) from an estimated 350,000 cases in 1988 to 1,998 reported cases in 2006 and reduced the number of countries that have never succeeded in interrupting WPV transmission to four (Afghanistan, India, Nigeria, and Pakistan). However, because vaccine-derived polioviruses (VDPVs) can produce polio outbreaks in areas with low rates of Sabin oral poliovirus vaccine (OPV) coverage and can replicate for years in immunodeficient persons, enhanced strategies are needed to limit emergence of VDPVs and stop all use of OPV once WPV transmission is eliminated. This report updates a summary of VDPV activity published in 2006 and describes VDPVs detected during January 2006-August 2007.

VDPVs can cause paralytic polio in humans and the potential for sustained circulation of poliovirus. VDPVs resemble WPVs biologically and differ from the majority of Sabin vaccine-related poliovirus isolates by having genetic properties consistent with prolonged replication or transmission. Because poliovirus genomes evolve at a rate of approximately 1% per year, Sabin vaccine-related isolates that differ from the corresponding OPV strain by more than 1% of nucleotide positions (usually determined by sequencing the genomic region encoding the major viral surface protein, VP1) are estimated to have replicated for at least 1 year after administration of an OPV dose. This is substantially longer than the normal period of vaccine virus replication of 4-6 weeks.

Poliovirus isolates can be distinguished by their three serotypes: type 1, type 2, and type 3. Isolates also can be divided into three categories, based on the extent of VP1 nucleotide sequence divergence from the corresponding Sabin OPV strain: 1) Sabin vaccine-like viruses (<1% divergent), 2) VDPVs (1%-15% divergent), and 3) WPVs (>15% divergent) (4). VDPVs are further categorized as 1) circulating VDPVs (cVDPVs), which emerge in areas with inadequate OPV coverage; 2) immunodeficient-associated VDPVs (iVDPVs), which are isolated from persons with primary immunodeficiencies who have prolonged VDPV infections after exposure to OPV; and 3) ambiguous VDPVs (aVDPVs), which are either clinical isolates from persons with no known immunodeficiency or environmental isolates whose ultimate source has not been identified.

Update on Vaccine-Derived Polioviruses Worldwide, January 2006-August 2007
MMR Weekly 2007 56: 996-1001

Related:

• Epidemics to eradication: the modern history of poliomyelitis
• Imaging Poliovirus Entry in Live Cells