Orthomyxoviruses

Influenzae A,B &C

4/3/13

A and B cause disease in humans, C infects humans, but does not cause disease

A also frequently infects animals

B only infects humans and causes less severe symptoms

-RNA viruses-means they are enveloped

Very similar to Paramyxoviruses except genome is segmented

            8 segments-encoding 10 products

Have HA-plays role in attachment and fusion

Neuraminidase-cleaves sialic acid of host molecules

Both HA and N exist as trimers

Ortho enters through coated pit formation.

Infection and replication-

            Attach to host sialic acid by Hemagglutinin

            Taken in by endocytic vesicle

            Decrease in pH causes conformational change in HA that facilitates fusion

of viral envelope with vesicle wall

M2 (found only in type A) promotes further acidification which allows
dissociation of NP from matrix and RNA

            Genome released into cytoplasm

            RNA migrates to nucleus where transcription takes place (mRNA & cDNA)

                        mRNA goes back to cytoplasm for translation

                        Replication using + strand template takes place in nucleus

                        High concentrations of NP will shift production to cDNA

            NP, PA, PB1 and PB2 migrate into nucleus and attach to -RNA segments

            HA, NA and M2 go via endoplasmic reticulum for surface expression

            Matrix protein lines the inside of cell

            Assembly and budding-not very effective due to random assortment of segments

 

Flu- Respiratory tract infection

            “Stomach flu” is usually rotavirus, enterovirus, or adenovirus

            symptoms include severe malaise, fever, myalgia, substernum pain, photophobia

            Can lead to bacterial or viral pneumonia

            Causes loss of ciliate tissue in URT

Host response directed against HA and NA molecules

            Both undergo genetic drift-subtle mutations

            Occasionally undergo genetic shift-rapid only in A

Designation-

            There are 15 known serotypes of hemagglutinin and 9 serotypes of neuraminidase

            These can occur in random combinations (some are much more prevalent than others)

            Includes virus type; location, month, and year of initial isolation; specific hemagglutinin and neuraminidase types if known

            A/Bangkok/1/79 (H3N2)

            B/HongKong/2/83 (H2N1)

            A/HongKong/7/03 (H5N1)

 

Host specificity, co-infection and antigenic shift

Host specificity is determined by sialic acid binding of HA

Single amino acid seems to determine specificity

If HA aa 226 is leucine humans can be infected

If HA aa 226 is glutamine birds can be infected

Pigs can be infected by both

Coinfection happens when a single cell is infected with two different viruses

            Typically pigs infected with human and avian viruses

            Allows genetic rearrangement and genetic shift

            Genetic Shift-

            Result of segmented genome and packaging

            Associated with epidemics

                        Dramatically different virus emerges in short time

Prevention and treatment

            Vaccine-produced annually based on three most likely serotypes

                        Very young and very old should be vaccinated

                        Those in the middle need to balance risk/benefits

 

            Hand washing during flu season

                        Virus is very labile and will become noninfectious within 2 hours

                        Frequent hand washing will decrease transmission from surfaces

 

            Treatment-

                        Amantadine and rimantadine

                                    Inhibit ability of M2 to decrease pH

                                    May effect ion channels

                        Tamiflu and Zanamivir inhibit neuramindase activity

                                    Zanamivir is inhaled, Tamiflu is taken orally

                                    Both diminish the severity and duration of infection

                                    Must be taken within first 12 hours of symptoms

 

Avian Flu

            Binding affinity to SA 2,3 Gal rather than SA 2,6 Gal from avian strains

            Strains from infected humans demonstrate mutations allowing binding to SA 2,6 Gal

 

            Already resistant to Amantadine and rimantadine

                       

            5/1/05  President signed executive order authorizing strict quarantine measures if strains capable of causing pandemic flu come to U.S.