MICROBIO 2.5 - NAKED RNA VIRUSES

• Naked RNA viruses

Eradicating Smallpox vs. Monkeypox

• Smallpox eradication stemmed from specific viral and disease characteristics, plus successful vaccination and quarantine.
• Smallpox had an exclusive human host range, negating animal reservoirs or vectors.
• Only one serotype existed wherein immunization protected against all infections.
• Antigenic determinants are shared with other pox viruses.
• Smallpox presented consistently with visible pustules, simplifying contagion source identification for quarantine and vaccination.
• Immunization with animal poxviruses guarded against smallpox.
• The smallpox vaccine was stable, inexpensive, and easy to administer.
• Vaccination success was indicated by a visible scar.
• The World Health Organization (WHO) led a successful global campaign that combined vaccination with quarantine contributing to eradication.

RNA Viruses and DNA Viruses

• RNA viruses can be either enveloped or non-enveloped.
• Non-enveloped RNA viruses include astroviruses, reoviruses, caliciviruses, picornaviruses, and rotaviruses.
• Enveloped RNA viruses include togaviruses, flaviviruses, coronaviruses, retroviruses, lentiviruses, rhabdoviruses, oncoviruses, paramyxoviruses, arenaviruses, bunyaviruses, and orthomyxoviruses.
• Rota is a subtype of Reo virus.
• There are not negative-sense naked RNA viruses.

DNA Viruses

• DNA viruses also exist as both non-enveloped and enveloped types.
• Non-enveloped DNA viruses encompass parvoviruses, adenoviruses, and papillomaviruses and polyomaviruses.
• Enveloped DNA viruses are herpesviruses, poxviruses, and hepadnaviruses.

Why Study Naked RNA Viruses?

• Norovirus is a leading cause of epidemic and sporadic gastroenteritis, described in 1979 as "Winter Vomiting Disease".
• Described as a contagious virus the norovirus causes vomiting and diarrhea.
• Direct contact, consuming contaminated food/water, or touching contaminated surfaces facilitate Norovirus transmission.
• Norovirus is often called "winter vomiting disease" because of its seasonality.
• Contagious norovirus causes nausea, vomiting, diarrhea, and abdominal pain.
• Transmission happens via direct contact, or contaminated food/water surfaces.
• Norovirus constitutes a leading cause of foodborne illnesses.
• Rotavirus mortality rates in children under 5 exhibit geographic disparities.
• Polio eradication efforts show substantial progress globally from 1988 to 2019.

Polio

• Currently, inactivated poliovirus vaccines are used.

Class Objectives

• Understand the differences between naked and enveloped RNA viruses compared to DNA viruses in structure, replication, and morphology.
• Articulate the concept of "sense" in virology.
• Compare and contrast naked and enveloped RNA viruses.
• Identify naked RNA viruses and the diseases they cause.
• Diagnose naked RNA virus infections based on signs, symptoms, and diagnostic tests.
• Prescribe suitable prevention and treatments, including available vaccinations and therapeutics.
• Naked RNA viruses of significance include Caliciviridae, Picornaviridae, and Reoviridae.
• Astroviridae causes self-limiting gastroenteritis in children, particularly those with weakened immune systems.

Virus Families

• Key characteristics of Caliciviridae, Picornaviridae, and Reoviridae:
• Caliciviridae features include ssRNA, linear shape, positive sense, and icosahedral capsid; includes Norwalk/Norovirus.
• Picornaviridae features include ssRNA, linear shape, positive sense, and icosahedral capsid; Enterovirus, Poliovirus, Rhinovirus and Coxsackie are examples.
• Reoviridae features include dsRNA, linear shape, N/A sense, icosahedral capsid; Rotavirus, and Orthoreovirus are examples.
• Double-stranded viruses contain both positive-sense and negative-sense strands.

Viral Life Cycle

• Viruses bind to specific receptors.
• Naked viruses use surface-exposed capsid regions/proteins for attachment.
• Virions move along the host cell surface to find entry receptors.
• Viruses may enter cells through endocytosis, followed by uncoating.
• Some viruses attach to cells and are "phagocytized" via viropexis, involving picorna, papilloma, and polyoma viruses.
• Uncoating disassembles virions, releasing the viral genome for cellular transcription and translation.
• Most RNA viruses including retroviruses are transcribed and processed in the cytoplasm.

Replication

• RNA viruses typically replicate in the cytoplasm,.
• dsRNA viruses such as Reo/Rota use viral RNA polymerase to transcribe +ssRNA, which is then translated into proteins.
• ssRNA's classification hinges on its RNA polarity.
• Positive-sense strands act as mRNA and are directly translated by cellular ribosomes. Examples: Caliciviridae, Picornaviridae, and Astroviridae
• Naked positive-sense viral genomes are infectious on their own.
• Naked negative-sense strand viral genomes are not infectious by themselves.

Assembly

• Viruses typically release via lysis because they are naked
• Self-assembly of genomic and structural proteins forms the nucleocapsid.
• Assembly involves progeny viral RNA, early and late proteins, & capsid.
• Lysis of the cell is a common release method for naked viruses.

Key Concepts

• Rotaviruses: are wheel-shaped, and double-stranded RNA viruses.
• Noroviruses are small, single-stranded RNA viruses that currently cannot be cultivated.
• Other viruses can also cause viral gastroenteritis like enteric adenoviruses, sapoviruses, astroviruses, and Aichi virus.
• Noroviruses are a leading cause of viral gastroenteritis in adults and the second leading cause of severe disease in children. Associated with disease in schools, nursing homes, vacation settings, military ships, restaurants, catered meals, and hospitals.
• Peak incidence occurs in winter months in North America.

Caliciviridae

• Comprise single-stranded, positive-sense RNA genomes.
• Icosahedral shape and spikes on the surface.
• The name "Norwalk virus,” comes from the first identified species in Norwalk, Ohio in 1970.
• Calicivirus is referred to as Norovirus today.
• "Winter vomiting bug" describes its seasonality and effects.

Norovirus

• The disease is a leading cause of epidemic and sporadic gastroenteritis.
• It accounts for ~20 million gastroenteritis cases in the United States annually.
• Primary symptoms include vomiting, watery diarrhea, and stomach pain.
• Self-limiting, resolving in approximately 3 days, but severe cases are seen in the very young, very, old and immunocompromised.
• The virus transmits via the fecal-oral route, often through contaminated water or food.
• Low infectious dose needed for infection.
• Prolonged viral shedding promotes host-to-host transmission.
• It is genetically diverse allowing for reinfection by different strains.
• Prevention through sanitation with no vaccine exists.
• Rehydration therapy provides the management.

Rhinovirus and Picornaviruses

• Picornaviruses are small, positive-sense RNA viruses, with enteroviruses and hepatitis A virus being examples.
• Enteroviruses include polioviruses, coxsackieviruses, echoviruses, rhinoviruses, etc.
• Named for infecting the gastrointestinal (GI) tract.
• After replication in the intestine, they shed through the stool over weeks or months.
• Polioviruses spread to the central nervous system from the GI tract.
• Enteroviruses target different organs.
• Outcome varies from asymptomatic infection, aseptic meningitis, to flaccid paralysis with systemic enteroviruses.
• Viral detection via nucleic acid amplification and culture identifies suspected polio.
• There are no treatments available.
• Preventable via inactivated (Salk) or attenuated (Sabin) vaccine.
• Person-to-person transmission occurs through contamination or areosols.
• Rhinoviruses bind to respiratory epithelial cells.
• Infections are generally mild, limited to the upper respiratory tract, but severe lower respiratory tract disease can result.
• Likely caused by mechanisms other than virus-induced cytopathology.
• Diagnosis isn't routine.
• No antiviral treatment exists and vaccine development is impossible due to the >100 serotypes.
• 4 genera of picornaviruses include viruses that cause human disease
• "Enterovirus" consists of 10 species, of which 7 contain human pathogens which are human enterovirus A-D & human rhinovirus A-C
• Types of non-polio enteroviruses can cause disease in humans.

Rhinovirus Cont.

• Human enteroviruses A-D begin in the alimentary tract, spreading through the blood to target organs.
• Clinical syndromes vary on the target organ
• Rhinovirus A-C infection begins in mucosal epithelium of respiratory tract
• Infections are limited to upper respiratory tract with types A & B human rhinovirus.
• Lower respiratory tract infections are involved with the virus type C
• Typically confined to the upper respiratory tract, which is the site of infection
• Infection triggers the innate immune system.
• Inflammatory chemokines & cytokines give rise to common cold symptoms.
• Antibodies offer temporary protection against the initiating serotype only.
• No vaccine exists due to the number of serotypes, therefore symptoms are managed using NSAIDs, decongestants, expectorants, and bronchodilators.

Poliovirus and Coxsackieviruses

• Three species of poliovirus exist.
• Infection is usually asymptomatic, although the central nervous system can be involved. (1 in 200 cases)
• The CNS via viremia and retrograde neuronal travel (retrograde: travels up towards/into brain).
• Replication happens in the spinal cord (motor neurons of anterior horn).
• Symptomatic infection causes meningitis, including temporary/permanent paralysis.
• Paralysis may be fatal if it involves the respiration muscles
• Post-polio syndrome can occur 30-40 years after initial poliomyelitis.
• Treatment with an "iron lung" = Emerson Respirator is an older device to aid breathing.

Polio Vaccines: Sabin

• Preventative vaccination.
• A live vaccine is Sabin (Infectious, Attenuated)
• Sabin has the benefit of being easy to administer, produces intestinal immunity, spreads to contacts and inexpensive.
• Sabin has higher risk in that the viral form may revert during intestinal replication (vaccine-associated poliomyelitis), not safe for immunodeficient persons

Polio Vaccines: Salk

• A live vaccine is Salk (Inactivated).
• Salk has the benefit when properly prepared does not cause disease and safe for immunodeficient persons
• Must be injected, produces reduced intestinal immunity compared with natural infection, and costly.
• Currently, the inactivated polio vaccine (IPV) is given to US children and at-risk adults. (travelers, laboratory & health care workers, etc.).
• A live attenuated oral polio vaccine (OPV) is still available in some countries.
• Herpangina is self-limiting, acute febrile illness primarily in with children with fever, vomiting, & small painful lesions or ulcers of the mouth. Ex: children with hand, food, & mouth.
• Coxsackieviruses include pleurodynia and Bornholm disease (Inflammation of pleura); Patients usually experience mild-severe muscle pain in thorax & abdomen, myyocarditis, particularly in newborns in newborns, paralysis, and Type 1 Diabetes which develops from the destruction of the pancreas.

Rotavirus

• Reoviridae covers the respiratory tract.
• It is transmitted by the fecal-oral route through person-to-person contact or ingestion.
• Susceptibility hinges on blood type and secretor status.
• These viruses do not invade the intestinal mucosa or spread to other organs.
• Viral induced changes in the small intestinal mucosa leads to diarrhea.
• A vaccine exists.
• Rotavirus is the most common cause of viral gastroenteritis in young children with peak incidence in US occurring during the winter months.
• Wheel-like morphology.
• Leads to severe diarrhea.
• Causes severe diarrhea in children/infants, but can lead to death if dehydrated.
• The virus has enterotoxin-like effects
• NSP4 protein increases enterocyte cytoplasm calcium concentration, which leads to changes in cytoskeleton and promotes water & electrolyte loss (diarrhea) which can lead to severe morbidity or even death.
• Vaccination is advised for all infants.
• Dorothy Horstmann discovered the poliovirus travels through blood to get to the brain.
• Isabella Morgan proved that inactive virus could be given to a money to prove it could stop live virus.