Viral Ecology & Pathology

Influenza virus is transmitted from person to person in droplets released by sneezing and coughing. Some of the inhaled virus lands in the lower respiratory tract. The cough may be persistent but the most prominent symptoms of influenza are systemic: fever, muscle aches.

Vaccines: Isolated HA gives good serological protection (estimated at 60-80%). Vaccines are produced by reassortment of egg-adapted strains with the required HA type. Large amounts of virus are then grown in embryonated eggs, being purified and formalin inactivated. The amount of doses given to a patient depends on the age of patient.

Picture extracted: http://www.microbiologybytes.com/virology/Orthomyxoviruses.html

References to text (Orthomyxoviruses)http://www.ipedia.net/information/Orthomyxoviridae http://www.microbiologybytes.com/virology/Orthomyxoviruses.html

Reproductive Cycle of an Orthomyxoviridae in a Host Cell

Orthomyxovirus replication is depending on the presence of active host cell DNA, and also the virus RNA. It takes about 6 hours for the replication of the orthomyxovirus.

1. The virus attaches to the cells, which binds to cell membrane, containing acid which are the receptor for virus adsorption.

2. The virus is then engulfed by pinocytosis into endosomes.

3. The acid environemnt of the endosome causes the virus envelope to fuse with the plasma membrane of the endosome, uncoating the nucleocapsid and releasing it into the cytoplasm.

4. A transmembrane protein derived from the matrix gene (M2) forms an ion channel for protons to enter the virion and destabilize protein binding, allowing the nucleocapsid to be transported to the nucleus, where the genome is transcribed to yield viral mRNA.

5. The virus scavenges cap sequences from the nascent mRNA generated in the nucleus by transcription of the host DNA and attaches them to its own mRNA.

6. The viral mRNA was transported to the cytoplasm by those cap sequences, where it is translated by host ribosome.

7. The nucleocapsid is assembled in the nucleus.

8. The viral envelope hemagglutinin is subjected to proteolytic cleavage by host enzymes during budding. This process is necessary for the released particles to be infectious.

9. Newly synthesized virions have surface glycoproteins that contain N acetylneuraminic acid as a part of their carbohydrate structure.

picture extracted: http://www.microbiologybytes.com/virology/Orthomyxoviruses.html

Virion Structure of a Orthomyxoviridae

The virions of an orthomyxovirus consist of:

1. An envelope
2. A matrix protein
3. A nucleoprotein complex
4. A nucleocapsid
5. A polymerase complex.

• The virus capsid is enveloped.
• The virions can be in spherical, pleomorphic or filamentous forms.
• They are 80-120 nm in diameter and 200-300 nm long.
• The surface projections are densely dispersed, hemagglitinin-esterase (HEF) spikes, or spaced widely apart, hemagglutinin (HA) spikes.
• There are about 500 spikes evenly dispersed or clustered and are covering the surface comprising hemagglutinin, neuraminidase, or esterase-esterase.
• The surface projections are composed of one or different types of proteins and are 10-14 nm long and 4-6 nm in diameter.

The nucleocapsid is elongated with helical symmetry and is segmented with loops at one end.

Picture extracted from: http://pathmicro.med.sc.edu/mhunt/RNA14.jpg

Genome Structure

The genome of the orthomyxovirus consists of six to eight segments of linear, negative-sense, single-stranded RNA. The complete genome is 10000-14600 nucleotides long.

• Segment 1 is fully sequenced and the complete sequence is 2300-2500 nucleotides long.
• Segment 2 has the same sequenced and length as Segment 1.
• Segment 3 is also sequenced, but only estimated, and the complete sequence is 2200-2300 nucleotides long.
• Segment 4 has been completely sequenced and the complete sequence is 1700-1800 nucleotides long.
• Segment 5 has been sequenced, but only estimated, and is 300-1900 nucleotides long.
• Segment 6 has been sequenced, but only estimated, and is 1400-1500 nucleotides long.
• Segment 7 has been sequenced, but only estimated, and the complete sequence is 800-1100 nucleotides long.
• The genome has terminally redundant sequences and the sequence is repeated at both ends. The sequence has conserved regions in all RNA species or some RNA segments.

The multipartite genome is encapsulated with each segment in a separate nucleocapsid, and the nucleocapsids are surrounded by one envelope. Each virion contains defective interfering copies.

Orthomyxoviridae

Under Orthomyxoviridae, there are Influenza virus types A and B. They are common causes of acute respiratory illnesses. Both virus types may cause epidemics of considerable morbidity and mortality.

• Influenza virus A causes of all flu pandemics and infect humans, other mammals and birds
• Influenza virus B infect humans and seals
• Influenza virus C infects humans and pigs.

Influenza A virus

Influenza B virus

Influenza C virus

Picture extracted: http://www.ioe.ucla.edu/Ctr/research/AvPath/avian_influenza.html
http://www.argene.com/pictures_gallery/index_ang.php?o=300
http://pathmicro.med.sc.edu/mhunt/flu.htm