- RNA Viruses

These viruses must transcribe RNA into a + strand to act as mRNA Virus brings along a copy of the RNAdep RNA pol (replicase) in the virus capsid Recently discovered gene in eukaryotes that is RNA replicase, not enough produced to help viruses

More diversity in this group than the + RNA viruses Typically genomes are larger than the + RNA viruses as well Because long strand of RNA is fragile, genomes may be segmented Not infectious as isolated RNA (unlike + RNA viruses)

Some of these viruses are defined as ambisense Genome can be read in both directions (at least in part) Typically have very complicated life cycles

Four families of RNA viruses package genomes as single piece of RNA Or monopartite

Assigned to superfamily Mononegavirales: Rhabdoviridae Paramyxoviridae Filoviridae Bornaviridae

Rhabdoviridae:

More than 150 viruses of vertebrates, invertebrates and plants Distinctive bullet-shaped morphology of virion Includes rabies virus and vesicular stomatitis (of horses)

Rabies one of the oldest and most feared diseases of man and animals Two genera infect mammals:

Vesiculovirus - vesicular stomatitis virus

Lyssavirus - rabies Helical nucleocapsid enclosed in bulletshaped envelope w/ matrix proteins

Terminal repeats which allow panhandle formation of genome Genome about 11 - 12 kb

Primary transcription produces 5 monocistronic mRNAs which are 5 capped and 3 tailed
But only single promoter sequence

Fig. 16.1

Virion is brought into cell by RME and not completely uncoated Replicase is associated with virion and produces capped mRNAs from genome Cap structure is same as eukaryotic, but different bond formed Poly A tail added by stuttering of enzyme complex

Fig. 16.3

Enzyme can continue to transcribe into mRNA or may fall off Therefore get different levels of the 5 proteins Largest quantity of N (first), smallest quantity of L (last) When level of N builds up, newly synthesized RNA binds to it

Association of +RNA and N protein means stuttering doesnt happen Full length + RNA will be produced to use as template for new RNA N protein also interferes with protein movement into and out of nucleus So host cell is shut down

Paramyxoviridae:

Originally classified with Orthomyxoviruses (influenza) Share some characteristics: hemagglutination neuraminidase
However, genome and replication are different

Subdivided into two subfamilies with 4 genera Paramyxovirus - Sendai virus

Parainfluenza virus some infect humans Rubulavirus - mumps

Morbillivirus - measles
Pneumovirus - respiratory syncytial virus

Enclosed by lipid envelope which is extremely fragile 15 - 16 kb of ss - RNA

6 - 10 genes, most structural proteins

Interesting glycoprotein spikes in membrane hemagglutinin (H spikes) neuraminidase (N spikes)

Many of the diseases in this group are considered childhood diseases Several are generally harmless in children, but may be much more severe in adults RSV extremely severe in infants, measles can be too Measles actually infects all ages

Fig. 16.4

Filoviridae:

First discovered in 1967 when vaccine workers in Marburg, Germany were infected
7 out of 25 died

In 1976, outbreak in Zaire and Sudan had higher mortality rate (50-90%) called Ebola

Have had sporadic outbreaks since mortality rate varies Third virus Ebola Reston infects primates, but apparently does not cause disease in humans Genome about 19 kb and encodes polymerase and 6 structural proteins 5 Pol-VP24-VP30-G-VP40-VP35-NP 3

Bornaviridae:

Cause variety of neurological symptoms in warm-blooded vertebrates About 9 kb, encodes 6 genes
mRNAs are capped and tailed Only non-segmented RNA virus that uses nucleus as site of replication

Some bornavirus + RNAs made in nucleus are spliced But caps are put on by viral polymerase, not cellular Think that some bornaviruses may play a role in mental illness

Orthomyxoviridae:
Another historically important virus (influenza) Pandemic in 1918 killed more than 20 million people more than WWI 3 types A, B and C A most common (also 1918 strain) B less common C even less common

Enveloped RNA virus, but with some differences:

Virion roughly spherical, but may see pleomorphism, including filaments HA and NA spikes on surface of envelope 8 segments of genome, each coding for 1 protein (except the 2 smallest with 2 each)

RNA molecules weakly encapsidated into helical nucleocapsids Transcription of RNA occurs in nucleus (unlike most other RNA viruses) Flu replicase cannot cap mRNAs so need cellular cap as a primer Replication must occur in nucleus so cap snatching or stealing can occur

Also, flu uses splicing mechanisms of nucleus for its own mRNAs So 10 mRNAs are made from the 8 segments of influenzas genome 2 viral pol subunits required for mRNA synthesis, for cap binding and cleaving functions

Once viral NP made, new genomes are made

Also have to make sufficient copies of pol to package in new virions Do not know details of switch from making mRNA to making genomic RNA Problem for influenza comes with packaging have to get 8 segments into one capsid

Frequently mistakes are made DI particles may be generated

Influenza changes frequently and sometimes drastically

Antigenic drift vs. antigenic shift Drift due to accumulation of random mutations Shift due to recombination of segments among 2 different flu viruses

Humans have receptors for swine influenza viruses So can get recombination of swine/human virus But swine also have receptors for avian viruses Chance for avian influenza to jump to humans completely new virus (1997)

HA and NA spikes are important in classification and attachment

14 HA subtypes 9 NA subtypes

Can recombine into various patterns that emerge every year HA important in attachment to sialic acid

Bunyaviridae:

Often considered sense viruses, but some are ambisense Large group of about 350 mainly arthropod-transmitted viruses Occur most frequently in tropical countries

Most never infect humans or domestic animals 5 genera of animal bunyaviruses: Bunyavirus La Crosse Hantavirus Sin Nombre Phlebovirus Rift Valley fever Nairovirus Crimean-Congo HF Tospovirus plant viruses

Capsids have helical symmetry, inside envelope 3 separately encapsidated segments of ssRNA (tripartite) L M S Sizes within those can vary widely RNA and protein complex to form nucleocapsids

RNA is linear, but may appear circular due to base pairing at ends mRNAs are made with 5 cap but no 3 tail (cap snatching outside nucleus) S segment of some genera (Phlebovirus and Tospovirus) is ambisense Means ORFs arranged in opposite directions

Fig. 16.9

After infection, subgenomic mRNAs are transcribed from all 3 segments Requires virion-associated RNA-dep RNA pol After translation, replication of virion RNA occurs

Four kinds of diseases caused by Bunyaviruses: Encephalitis Hemorrhagic fever Hemorrhagic fever with renal involvement Hemorrhagic fever with pulmonary involvement (HARDS)

Arenaviridae:

Usually produce mild and persistent diseases in natural mammalian host Can cause lethal hemorrhagic fevers in primates (Lassa fever) Family gets name from appearance: ribosomes in virions

Arena is Latin for sand = sandy appearance Envelope surrounds 2 nucleocapsid segments (bipartite) Genome is 2 linear segments L and S Both segments have ambisense organization

Family contains one genus Arenavirus divided into 2 serogroups Old World and New World

After infection, subgenomic mRNAs made Caps added from host mRNA, no tails