RNA Viruses: Picornaviruses, Orthomyxoviruses & More

Clinical virology PICORNAVIRUSES Properties 1. Very small in size (Pico = small), (smallest RNA viruses). 2. non-enveloped ss RNA viruses with icosahedral symmetry. 3. Replication and maturation occur in the cytoplasm. 4. On tissue culture, they cause granulation and rounding of infected cells (CPE)...

Clinical virology PICORNAVIRUSES Properties 1. Very small in size (Pico = small), (smallest RNA viruses). 2. non-enveloped ss RNA viruses with icosahedral symmetry. 3. Replication and maturation occur in the cytoplasm. 4. On tissue culture, they cause granulation and rounding of infected cells (CPE). FOOT AND MOUTH DISEASE (FMD) VIRUS This highly infectious disease of cattle, sheep, pigs and goats. May be transmitted to human by contact with infected animals or ingestion of contaminated meat, milk or milk products. Clinical features: In human, the disease is characterized by fever, salivation, vesicles on mucous membrane of oropharynx and on the skin of the palms, soles, fingers and toes. ORTHOMYXOVIRUSES Ortho = direct and Myxo = mucous, viruses in this Family have direct affinity for mucous membrane. Influenza viruses Common characteristic: 1- There are three antigenic types of influenza viruses: A, B and C. 2- Virions are pleomorphic (spherical or filamentous). 3- The genome is ss RNA, is segmented. consists of 8 different helical segments in type A & B and 7 segments in type C. 4- The virus is enveloped with 2 types of spikes projecting from it, the haemagglutinin (HA) and the neuraminidase (NA). ▪ Antigenic variation is common in influenza viruses due to antigenic changes in HA and NA. 1  The envelope has 2 types of glycoprotein surface spikes: ❖ Haemagglutinin (HA): ✓ There are 16 types in animals and 8 types in human ✓ Rod shaped and have several functions: a) Attachment of the virus to cell surface receptors. (sialic acid) and entry of the virus into the cells. b) Stimulate a protective neutralizing antibody immune response. c) Agglutinate human and Chicken RBCs in the laboratory (Haemagglutination assay). ❖ Neuraminidase (N): ✓ It contains 9 types in animals and 6 in humans. ✓ Mushroom shaped and facilitate virus release from infected cells during budding and degrades the protective mucous layer. Antigenic variation is common in influenza viruses due to antigenic changes in HA and NA. Antigenic Variation Antigenic shift Antigenic drift (Major Ag Variation) (Minor Ag Variation) Major antigenic changes resulting from genome Due to accumulation of mutation in the gene reassortment between different virus strains and resulting in amino acid changes in the protein. occurs only for influenza A. It occurs every year causing local outbreaks of influenza A and B infection. Antigenic shift occurs infrequently every 10 years. Influenza B is predominantly a human virus and doesn't undergo antigenic shift. 2 Genetic re-assortment: It is the exchange of segments between the segmented nucleic acid of two different strains of viruses infecting a single cell. As a result, some of the progeny viruses will contain a mixture of gene segments from both strains. Features Antigenic Shift Antigenic Drift Frequency Every 10 years Every year Degree of change Major Minor Mechanism Genetic re-assortment Point mutations in the RNA genome Cause epidemics & Effect Cause local outbreaks of influenza pandemics Pathogenesis: Infection occurs by droplets and contact with contaminated hands or surfaces. The virus multiplies locally in respiratory tract causing rhinitis, pharyngitis and bronchitis. The disease is self limited It may be complicated by viral or bacterial pneumonia due to H. influenza, Strept. pneumoniae and Staph. aureus mainly in the elderly or debilitated individuals. Prophylaxis: Inactivated vaccine containing two types of strain A and one type of strain B virus from the previous winter is produced every year. This vaccine is not fully effective, it is protective only in 70% of cases and immunity is short lasting because: ❖ Antigenic variations and emergence of new strains that is not present in the vaccine. For such reasons the vaccine is reformulated every year to contain the current antigenic strains. Yearly boosters are recommended before the flu season i.e., October and are given to the elderly, those with chronic disease, or to those who wish to reduce the risk of their acquiring influenza. 3 PARAMYXOVIRUSES Properties: 1. Enveloped ss RNA viruses. 2. The viral genome is linear and non-segmented. 3. Has 2 types of spikes, haemagglutinin (HA) and fusion (F) glycoprotein which mediates membrane fusion. a. MUMPS VIRUS (Infectious Parotitis) ‫التهاب الغدة النكفية‬ It is an acute generalized viral disease characterized by fever, swelling and tenderness of the parotid and sometimes the submaxillary glands. Transmission: ▪ Droplet infection. ▪ Direct contact with saliva and urine. Incubation Period: 12- 18 days Prevention: Vaccination with living attenuated vaccine. ▪ Live attenuated mumps virus vaccine given in combination with measles and rubella (MMR). ▪ It is given in 2 doses S/C one at 15 months of age and the 2nd just before school entry. It gives long lasting immunity ▪ Immunity: Is permanent (long life immunity) after a single infection. This is due to the presence of only one stable antigenic type and the neutralizing antibodies (IgM and IgG) formed are protective. 4  b. MEASLES VIRUS ‫فيروس الحصبة‬ Measles is an acute, highly infectious disease characterized by prodromal fever, conjunctivitis, cough and Koplik's spots. Koplik's spots : which are bluish white ulcers in the buccal mucosa opposite the upper molars. Maculopapular rash all over the body appears after the fever subsides. Transmission: Droplet infection. Direct contact or by the use of contaminated articles. Prevention: Immunization using Live attenuated measles virus vaccine given in combination with mumps and rubella as MMR vaccine. It is given in 2 doses S/C one at 15 months of age and the 2nd just before school entry. It gives long lasting immunity. Immunity: Long lasting immunity occurs after a single infection, and this is due to the presence of only one stable antigenic type and the neutralizing antibodies (IgM and IgG) formed are protective. It causes 2 types of infections: a. Postnatal rubella: Transmitted by droplet infection from person to person Incubation period: ranges from 2-3 weeks. Characterized clinically by low grade fever, malaise, maculopapular rash on the face and trunk, pharyngitis and joint pain. Viremia develops after 7-9 days & lasts for 13-15 days leads to the development of antibodies which rises as the rash fades. IgG antibodies persist for life providing solid immunity. (Lifelong immunity( b. Congenital rubella syndrome: ▪ Caused by transplacental transmission of infection to the fetus. ▪ It causes high rate of congenital anomalies that may end with fetal death or abortion. Treatment: ✓ Rubella is a mild self-limited illness. Prevention and control: Living attenuated rubella virus vaccine alone or in combination with measles and mumps (MMR). 5  RETROVIRUSES Properties: 1. enveloped ssRNA virus. 2. The envelope is formed of a lipid bilayer. 3. They contain the reverse transcriptase (RT) enzyme which converts the RNA into DNA. Human immunodeficiency virus (HIV) that causes AIDS is the most important member of this family. HUMAN IMMUNODEFICIENCY VIRUS (HIV) Acquired immunodeficiency syndrome (AIDS) Properties 1. The virus is ssRNA virus. 2. It has cone-shaped capsid made of protein called p24. 3. The core contains the viral genome, reverse transcriptase. 4. The envelope is composed of a lipid bilayer with viral glycoprotein projection called gp 160. Transmission: a) Blood transfusion using infected blood or blood products. b) Sexual intercourse. c) After a prick by contaminated syringes. d) From mother to infants: transplacental, during birth or via breast-feeding. e) Through contaminated tattoo needles, razors or ear-piercing implements. Pathogenesis: HIV infects CD4+ receptor-bearing cells (T-helper cells) and kills them resulting in suppression of cell-mediated immunity: The infected CD4+ cells fuse with neighbouring uninfected cells. This is followed by lysis of large numbers of fused cells with rapid fall of CD4+ helper cells count below 200 cells/μl (Normal = 500- 1500). Severe immune suppression that follows progressive HIV infection results in development of acquired immune deficiency syndrome (AIDS). Oral manifestations o f HIV infection HIV reduces immune response within oral cavity. This creates conditions for local oral manifestations of opportunistic infections and tumours: Among the most common infections are Periodontal disorders of poly microbial origin 6 Prevention and control: 1) Screening for blood in all blood banks to exclude any positive samples. 2) Care in handling blood or blood products and tissue specimens. 3) Use disposable syringes. 4) Toothbrushes, razors should not be shared. 5) Dental and surgical instruments should be thoroughly sterilized. 6) Safe discards of contaminated needles. 7) Immediate administration of antiviral drug to staff that has been accidentally infected via skin pricks. 8) HIV infected pregnant females should deliver by caesarean section. 9) Vaccination: are under trials. CORONAVIRIDAE Properties: Enveloped, helical, ssRNA Hemagglutinin molecules make up peplomers on virus surface, which give shape like sun with corona. Coronavirus Second most common cause of the common cold. Reservoir: birds and small mammals Transmission: respiratory droplets; virus also found in urine, sweat, and feces; original case is thought to have jumped from animal to human. Disease: severe acute respiratory syndrome (SARS), Atypical pneumonia Clinical case definition includes fever of >38.0 C , flu-like illness, dry cough, dyspnoea, and progressive hypoxia. Chest x-ray may show patchy distribution of focal interstitial infiltrates. 7  Transmission of SARS: The primary mode of transmission of SARS-CoV-2 is via 1. Exposure to respiratory droplets, from close contact or droplet transmission from asymptomatic, or symptomatic individuals harboring the virus. 2. Airborne transmission with aerosol-generating procedures 3. Fomite transmission from contamination of inanimate surfaces. Types of Covid-19 Immunization A) Active Immunization (Vaccination) RNA Vaccines (Moderna, Pfizer) Viral Vector vaccines (Oxford/AstraZeneca, Gamalaya-Sputnik) Inactivated Virus (SinoVac, SinoPharm) B) Passive Immunization (Antibody Administration) ❖ Approved corona virus vaccines: 1. Pfizer-BioNTech COVID-19 Vaccine 2. Moderna COVID-19 Vaccine 3. AstraZeneca Vaccine 4. Sinopharm's COVID-19 vaccine 5. Sinovac COVID-19 Vaccine Test yourself: MCQ 1. All the following are RNA enveloped viruses except: a) Foot and mouth disease virus b) Influenza virus c) Mumps virus d) Rubella virus 2. The main difference between orthomyxoviruses and paramyxoviruses is: a) The genome of orthomyxoviruses is segmented b) Orthomyxoviruses are enveloped viruses c) Paramyxoviruses are transmitted by droplet inhalation d) Orthomyxoviruses causes localized type of infection 3. Mumps is caused by: a) Ortho myxo virus b) Para myxo virus c) Rheno virus d) EB virus 4. A 3-year-old child presents at the physician’s office with symptoms of conjunctivitis, low grade fever and kolpik’s spots. The causative agent of this disease belongs to which group of viruses: a) Adenovirus b) Herpes virus c) Orthomyxovirus d) Paramyxovirus Complete: 1. Antigenic shift occurs in influenza virus because…………………… 2. Antigenic drift occurs in influenza virus is due to …………………. 3. The main function of HIV reverse transcriptase enzyme is………………. Discuss antigenic variation of influenza virus. 8