viruses

features of viruses in general:

Viruses differ from rickettsiae in that they all must convert to a non-infective 'eclipse phase' form during replication & that the synthetic processes during replication take place in the host cell cytoplasm & not within the organism itself as in all other classes of organisms.
A single virus particle, called a virion, is made up of a core consisting of a single molecule of nucleic acid, & a surrounding protein shell called a capsid.
Some viruses are also ensheathed in one or more outer membranes, or envelopes, composed predominantly of lipid, derived in part from the host cell or nuclear membrane prior to the release of the virus. Enveloped viruses are vulnerable to fat solvents such as ether or bile salts.
Larger viruses (esp. pox viruses), also contain carbohydratess, co-enzymes & even some enzymes (eg. lipase, catalase, phosphatase & polymerases) but none contain all enzymes necessary for its own metabolism thus all viruses are obligate intracellular parasites.
Plant viruses all contain RNA, whereas nearly all bacteriophages contain DNA.
Most RNA viruses contain a single strand (except reoviruses) whilst most DNA viruses contain a double strand (except parvoviruses).
many viruses shut off host cell RNA systems:¹⁾
- they do this to:
  - allow viruses to use host cellular machinery to preferentially translate viral proteins, replicate, and exit the cell
  - limit the host antiviral response by preventing the transcription, biogenesis, and/or translation of IFN and interferon-stimulated genes (ISGs) that can interfere with the viral replication cycle
- the mechanism they can use include:
  - translation shut-off, viruses can directly target host translation initiation by interfering with initiation factors or the ribosome
  - host antiviral response that suppresses the bulk of host translation as well
  - interfere with host RNA processing and thereby prevent host gene expression
  - activation of host-encoded proteins, for example, the latent endoribonuclease, ribonuclease L (RNase L)
  - triggering decay of host mRNAs

Transmissibility:

reproduction number = avg. number of secondary cases of disease generated by a typical primary case in a susceptible population
reproduction numbers for selected infectious diseases:
- pertussis (whooping cough) = 16-18
- COVID-19 coronavirus (2019-nCoV / SARS-CoV-2) = 4-15
- measles = 10-15
- polio = 8-12
- rubella = 6-7
- diphtheria = 6-7
- smallpox = 5-7
- mumps = 4-7
- SARS virus = 3 (excluding superspreaders)
- influenza seasonal = 1.5-3
- influenza pandemic = 2

Baltimore Taxonomy (abbreviated)

Viruses may be classified into 20 mammalian families by mode of replication:

DNA viruses:

Class I:

Double-stranded DNA → RNA polymerase → mRNA
Replicate via DNA polymerase;
Use host RNA polymerase (most):
- a) use host DNA polymerase:
  - adenoviridae
- b) have own DNA polymerase:
  - herpetoviridae - enveloped, 3 groups of human viruses:
    - neurotropic alpha group:
      - Herpes simplex virus (HSV)
      - varicella-zoster
    - lymphotropic, roseola beta group:
      - CMV, exanthem subitum: human herpesvirus-6 and human herpesvirus-7
      - HHV-5 aka CMV
      - HHV-6B spreads via saliva and infects nearly all children and causes roseola and febrile seizures
      - HHV-6A may account for 40% of unexplained infertility and 10% of all female infertility ²⁾
    - gamma group:
      - EBV / glandular fever / infectious mononucleosis,
      - human herpesvirus-8 (HHV-8 aka Kaposi's sarcoma-associated herpesvirus (KSHV))
        
        spread by saliva; usually asymptomatic but remains dormant in the body life-long but can reactivate in immunocompromised when it can trigger cancers via manipulating two human enzymes called CDK6 and CAD to reshape the way human cells produce new nucleotides ³⁾
        
        present in 100% of Kaposi's sarcoma tumours
        
        also causes primary effusion lymphoma, and HHV8-associated multicentric Castleman disease
        
        10% of North Americans and northern Europe have the virus while more than 50% of those in North Africa have it
  - hepadnaviridae
    - hepatitis B virus (partially ds DNA)
      - has reverse transcriptase activity
      - genomic replication via RNA intermed.!
  - papovaviridae (PApilloma, POlyoma, Simian Vacuolating Agent):
    - papillomavirus: human papilloma virus (HPV)
    - polyomavirus (non-enveloped) (see web article):
      - BK & JC viruses:
        
        transmission via oral/resp. route
        
        primary infection usually in childhood & causes mild respiratory illness then remain latent in urogenital tract
        
        asymptomatic reactivation & intermittent shedding of virus & uroepithelial cells in urine occurs spontaneously in immunocompetent persons but are more frequent in those with altered cellular immunity (eg. pregnancy, chemotherapy, HIV-1, allograft recipients)
        
        BK (disc. 1971 from immunosuppressed kidney transplant pt)
        
        worldwide seroprevalence in adults is 60-80%
        
        may cause haemorrhagic cystitis or BK viral nephropathy, but overt disease is rare & usually associated with immunocompromise
        
        reactivation appears to be cause of severe renal allograft dysfunction
        
        found in some human tumours but ? causal
        
        JC (disc. 1971 from pt with Progressive Multifocal Leukencephalopathy)
        
        causes Progressive Multifocal Leukencephalopathy esp. in immunocompromised pts
      - simian virus 40 (disc. 1961)
Have own RNA & DNA polymerase:
- poxviridae
  - do not have as much ability to mutate as RNA viruses
  - all share a DNA sequence with similar antigens that demonstrate cross-reactivity
  - their virulence and ability to escape the immune system are noteworthy
  - chordopoxvirinae
    - avipoxvirus (birds)
    - centapoxvirus (yoka pox)
    - cervidpoxvirus (mule deer pox)
    - crocodylidpoxvirus (Nile crocodile pox)
    - leporipoxvirus (myxoma pox)
    - molluscipoxvirus (molluscum contagiosum)
    - orthopoxvirus
      - variola (human smallpox SPX) - killed 300 million people in the 20thC with a mortality rate of 10-75%, eradicated (except in labs with risk of biological warfare use in populations now without herd immunity) in 1980 via vaccination
      - vaccinia (vesicular vaccinated lesions)
      - cowpox
      - monkeypox / mpox (MPVX) - squirrels, dormice, rodents, and non-human primates; human MPVX (H-MPVX)
      - Alaskapox - discovered in humans in 2015, can be fatal in the immunocompromised; potentially acquired from cat scratches;
      - buffalo pox
      - rabbit pox
      - racoon pox
      - camel pox
    - yatapoxvirus
      - tanapox (monkeys)
      - yabapox (monkeys)
    - suipoxvirus (swinepox)
    - parapoxvirus
      - pseudocowpox
      - orf (sheep)
    - capripoxvirus (goat pox, sheep pox, lumpy skin disease)
  - entomopoxvirinae - insect pox viruses

Class II: Single-stranded DNA

parvoviridae - Norwalk agent

RNA viruses:

unique as the only organisms that use RNA instead of DNA.
replication is complex & depends on whether contains single- or double- stranded RNA.
RNA that acts as mRNA is termed a positive strand.

Double-stranded RNA viruses:

Class III:
- Double-stranded RNA → viral RNA polymerase → mRNA
- reoviridae - reovirus, rotavirus, orbivirus (Colorado tick fever)

Single-stranded RNA viruses:

Class IV:
- Replication of plus-stranded viruses in which the input strand functions as mRNA:
  - picornaviridae:
    - enterovirus: poliovirus, Coxsackie, ECHO
    - rhinovirus
    - hepatitis A
    - cardiovirus
    - aphthovirus - foot and mouth virus
    - parechovirus - mostly mild rash/diarrhoeal illness but may cause severe neonatal illness involving CNS or causing a sepsis-like illness
  - togaviridae: - enveloped
    - rubivirus: rubella
    - alphavirus: Western equine encephalitis virus; Sindbis virus; Semliki forest virus;
  - flavaviridae:
    - flavivirus (flavus is latin for yellow):
      - relatively new viruses, derived from a common ancestor 10-20,000yrs ago & are rapidly evolving to fill new ecological niches
      - cause arboviral encephalitis
      - yellow fever virus; dengue virus; Japanese encephalitis; West Nile virus, Kunjin virus & Murray Valley encephalitis virus;
      - zika virus
    - hepacivirus:
      - hepatitis C virus, hepatitis G virus, GB virus
  - HepE
  - caliciviridae:
    - norovirus, sapovirus
  - astroviridae - non-enveloped causes infantile gastro.
    - arteriviruses
    - sequiviridae
    - nodaviridae - mainly non-human
  - Nidovirales - enveloped, positive-strand RNA viruses which infect vertebrates and invertebrates
    - large genome Nidovirales
      - Cornidovirineae
        
        coronaviridae / corona viruses (CoV)
        
        infectious bronchitis virus; OC43; mouse hepatitis virus;
        
        SARS virus;
        
        MERS virus;
        
        torovirus
      - Roniviridae - infect crustaceans
    - small genome Nidovirales:
      - Abnidovirineae
        
        Abyssoviridae - infect sea hares
      - Arnidovirineae
        
        Arteriviridae - infect vertebrates
        
        Variarterivirinae - mainly rodents
        
        Heroarterivirinae - mainly rodents
      - Mesnidovirineae
        
        Mesoniviridae - infect mosquitoes
      - Monidovirineae
        
        Mononiviridae - infect flatworms
      - Tornidovirineae
        
        Tobaniviridae - infect mammals, fish, snakes
        
        Torovirus - gastro in mammals
      - Nanidovirinae

Class V:
- Replication of minus-stranded RNA viruses in which mRNA is complementary to input RNA: (All enveloped)
- orthomyxoviridae: influenza
- order Mononegavirales:
  - paramyxoviridae:
  - paramyxovirus: parainfluenza virus, mumps virus
  - morbillivirus: measles virus
  - pneumoviridae:
    - human respiratory syncytial virus / human orthopneumovirus (HRSV)
    - human metapneumovirus (HMPV)
  - rhabdoviridae:
    - lyssavirus: Australian bat lyssavirus; rabies virus
  - filoviridae:
    - Marburg; Ebola virus disease (EVD);
  - bunyaviridae: bunyavirus: encephalitis viruses, haem.fever viruses; oropouche virus (Sth and Central America)
    - a biting midge in Sth America Culicoides paraensis can transmit the Oropouche virus which seems to be spreading in Central America in 2023-2024
  - arenaviridae: arenavirus: haem.fever viruses, Lassa fever virus, LCV

Class VI:
- RNA retroviruses → reverse transcriptase → DNA
- HTLV-1, HIV / AIDS

Typical Viral Genome Parts & Their Protein Products:

POL - reverse transcriptase (polymerase)
GAG - group antigen protein
protease
integrase
ribonuclease
ENV - viral coat protein
trans… activation
regulatory parts:
- eg. HIV: act on TAR part LTR
- NB. NF-KB from cytokines & HTLV-1 tax may also act on TAR → replication HIV;
virokines:
- esp. DNA viruses;
- act on non-infected cells to modulate progress of infection on body as whole:
- negate interferons/TNF;
- decrease inflammatory response;
- block complement pathway;
- stimulate metab. activity &/or prolif. nearby cells;
- decr. MHC I on cell surface (eg. adenovirus, poxvirus);
NB. DNA viruses tend to have 10-100's of genes whereas most RNA viruses have < 12, thus for vaccinia (DNA virus) 56 out of 198 Open Reading Frames are not required for replication in cultured cells & presumably they confer survival advantage by sabotaging host immune system;
Thus, typical RNA retrovirus genome:
- 5' - LTR — GAG — POL — ENV — xxx — LTR - 3'
  - where xxx = oncogene, etc;

International Committee on Taxonomy of Viruses (ICTV) Taxonomy

DNA viruses

Duplodnaviria

all double-stranded DNA viruses that encode the HK97 fold major capsid protein
Herpesvirales – the herpesviruses
Caudoviricetes – the tailed bacteriophages, which infect archaea and bacteria (prokaryotes)

Monodnaviria

all single-stranded DNA viruses that encode an endonuclease of the HUH superfamily that initiates rolling circle replication of the circular viral genome
includes the vast majority of identified ssDNA viruses, which are Group II: ssDNA viruses in the Baltimore classification system
Loebvirae - only infect bacteria
Sangervirae - only infect bacteria
Shotokuvirae
Trapavirae - only infect archaea

Adnaviria

includes archaeal viruses that have a filamentous virion (i.e. body) and a linear, double-stranded DNA genome

Varidnaviria

all DNA viruses that encode major capsid proteins that contain a vertical jelly roll fold.
these belong to Group I: dsDNA viruses of the Baltimore classification system
bacteriophages in Varidnaviria are potentially a major cause of death among marine prokaryotes.
The most notable disease-causing viruses in Varidnaviria are adenoviruses, poxviruses, and the African swine fever virus (ASFV)

RNA viruses

Riboviria

all viruses that use a homologous RNA-dependent polymerase for replication
Orthornavirae
- contains all RdRp-encoding RNA viruses, i.e. all dsRNA, +ssRNA, and -ssRNA viruses, often collectively called RNA viruses
Pararnavirae
- contains all RdDp-encoding viruses, i.e. all ssRNA-RT and dsDNA-RT viruses, collectively called reverse transcribing viruses
- Arterviricota
  - Revtraviricetes

satellite nucleic acids

Ribozyviria

a realm of satellite nucleic acids; presence of genomic and antigenomic ribozymes of the Deltavirus type.
Deltavirus - human hepatitis delta viruses

¹⁾

2024: Mechanisms and consequences of mRNA destabilization during viral infections

²⁾

http://www.eurekalert.org/pub_releases/2016-07/hf-ovf070616.php

³⁾

Nature 2024: Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus

OzEMedicine - Wiki for Australian Emergency Medicine Doctors

Table of Contents

viruses

features of viruses in general:

Transmissibility:

Baltimore Taxonomy (abbreviated)

DNA viruses:

Class I:

Class II: Single-stranded DNA

RNA viruses:

Double-stranded RNA viruses:

Single-stranded RNA viruses:

Typical Viral Genome Parts & Their Protein Products:

International Committee on Taxonomy of Viruses (ICTV) Taxonomy

DNA viruses

Duplodnaviria

Monodnaviria

Adnaviria

Varidnaviria

RNA viruses

Riboviria

satellite nucleic acids

Ribozyviria