Clinical Virology – RNA viruses

Orthomyxoviridae and Picornaviridae

Unique features of RNA viruses
- Central Dogma
- DNA -> RNA -> Protein
- Infectious ( +RNA viruses)
- Unusual characteristic
- Distinguish between viral mRNA and host mRNA

Overview of Picornaviridae
There are 5 genera:
- Aphtoviru
- Cardiovirus
- Enterovirus
- Heptovirus
- Rhinovirus

Morphology
1. Virions (naked)
2. Nucleocapsid isometric
3. Incomplete or empty capsids common

Genome of Picornaviridae
1. Genome RNA is infectious
2. One linear (+) RNA
3. Long not translated region end of 5’ end ‘clover leaf’ structure (IRES)
4. Single polyprotein of 2100 – 2400 aa
5. Modified ends


Picornaviridae – Rhinovirus

Pathogenesis
1. Upper respiratory tract infection
2. 2 – 3 days incubation
3. Endogenous IFN helps
4. Synthesized IgA, titer decline with time
5. Serum IgA persists for years
6. Over 100 rhinoviruses

Symptoms
1. Watery nasal discharge
2. Congestion
3. Sneezing
4. Slight/No fever

Lab diagnosis
1. Virus culture
2. Nasal washing
3. EIA
4. PCR

Epidemiology
- Throughout the year
- A few serotypes circulating at the same time
- Nasal discharge contains a lot of virus

Control
1. No vaccine. Cause it can recover easily.
2. Observe personal hygiene. Example: Wash hands; do not touch nose/eyes.
3. Sneeze onto tissue and throw away
4. Avoid people having cold, and stay home when with cold.

History of virus
1. 430B.C first report of influenza epidemic –Athens
2. 1918 – Flu pandemic (25 – 40 million deaths!)
3. 1957 – 1958 and 1968-1969 epidemics.

But now, flu vaccine are available but very expensive!


Overview of Orthomyxoviridae
Morphology
1. Spherical in shape
2. Enveloped
3. Pleomorphic
4. Spikes on envelope
5. Groups of Hemagglutinin(HA) or Neuraminidase(NA)
6. Ratio of Hemagglutinin: Neuraminidase; 5:1


Genome
1. 8 segments in RNA, ss(-)
2. Each segment contains 3 polymerase polypeptides
3. 5’ and 3’ end of all segemtns highy conserved

Influenza Virus – Pathogenesis
1. Analogy of the Hemagglutinin for receptors in the epithelium causes respiratory tracts in human
2. Hereditary resistance
3. Immunocompromised
4. Existing antibodies includes Anti-HA Ab and IgA, IgG
5. Macrophages, NK cells, cytokines

Lab Diagnosis
1. Throat
2. Virus culture
3. Direct EIA
4. PCR

Epidemiology
1. Viral Incubation last 1 to 4 days
2. Few known serotypes circulating simultaneously
3. Virus abundant when being discharge through means of nasal

Antigenic
A mutation in the genetic code of surface antigen meant there is a Antigenic Drift whereas when gene reassort from different sub-types, it’s known as a Antigenic shift. Under the Antigenic drift, there are minor changes in the genome both in Influenza genome A and B. Antigenic drift happens all the time as it occurs as a point mutation thus resulting in a new strain that can be fatal and poses a threat to mankind. On the other hand, Antigenic shift does major changes in the genome resulting in gene reassortment and thus, creating a new subtype instead of a new strain. However antigenic shift only happens in Influenza genome A as well as the fact that it happens occasionally and not all the time.

Strain naming for Influenza is whereby the Influenza virus get recorded down as follow B/California/37/96 (H1N1). The B marks the genome of the influenza, whether it is A or B genome. Follow by location whereby the virus is isolated, as shown above, California. The number 37 marks the number of isolate and lastly the year of isolation which is 1996.

Control
Vaccines are common amount cases of preventing infection of influenza. However, it’s often useless because of the continuous Antigenic drift/shift that occurs in the genome of Influenza virus. Another way of controlling the virus is through usage of Antiviral drugs whereby attachment of the virus to the receptors are prevented. A few more examples are as follow, Transcriptase inhibitors, RT inhibitors, Protease inhibitors and lastly Assembly of virions.