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GENERAL DESCRIPTION OF VIRUSES

A virus is a submicroscopic infectious agent that replicates only inside the

living cells of an organism. Viruses infect all types of life forms, from animals
and plants to microorganisms, including bacteria and archaea. Since Dmitri
Ivanovsky's 1892 article describing a non-bacterial pathogen infecting
tobacco plants and the discovery of the tobacco mosaic virus by Martinus
Beijerinck in 1898,  more than 9,000 virus species have been explained in
detail of the millions of types of viruses in the environment. Viruses are
found in almost every ecosystem on Earth and are the most numerous types
of biological entity. The study of viruses is known as virology, a
subspeciality of microbiology.

When infected, a host cell is forced to rapidly produce thousands of copies

of the original virus. When not inside an infected cell or in the process of
infecting a cell, viruses exist in the form of independent particles, or virions,
consisting of:

(i) the genetic material, i.e., long molecules of DNA or RNA that encode the

structure of the proteins by which the virus acts
(ii) a protein coat, the capsid, which surrounds and protects the genetic
material; and in some cases
(iii) an outside envelope of lipids. The shapes of these virus particles range
from simple helical and icosahedral forms to more complex structures.
Most virus species have virions too small to be seen with an optical
microscope, as they are one-hundredth the size of most bacteria.

The origins of viruses in the evolutionary history of life are unclear: some

may have evolved from plasmids—pieces of DNA that can move between
cells—while others may have evolved from bacteria. In evolution,
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viruses are an important means of horizontal gene transfer,

which increases genetic diversity in a way analogous to sexual
reproduction. Viruses are considered by some biologists to be a life
form, because they carry genetic material, reproduce, and evolve
through natural selection, although they lack the key characteristics, such
as cell structure, that are generally considered necessary criteria for life.
Because they possess some but not all such qualities, viruses have been
described as "organisms at the edge of life", and as self-replicators.

Viruses spread in many ways. One transmission pathway is through

disease-bearing organisms known as vectors: for example, viruses are
often transmitted from plant to plant by insects that feed on plant sap,
such as aphids; and viruses in animals can be carried by blood-
sucking insects. Influenza viruses are spread by coughing and
sneezing. Norovirus and rotavirus, common causes of viral gastroenteritis,
are transmitted by the fecal–oral route, passed by hand-to-mouth contact
or in food or water. The infectious dose of norovirus required to produce
infection in humans is less than 100 particles. HIV is one of several viruses
transmitted through sexual contact and by exposure to infected blood. The
variety of host cells that a virus can infect is called its "host range". This can
be narrow, meaning a virus can infect few species, or broad, meaning it is
capable of infecting many.

Viral infections in animals provoke an immune response that usually eliminates

the infecting virus. Immune responses can also be produced by vaccines, which
confer an artificially acquired immunity to the specific viral infection. Some
viruses, including those that cause AIDS, HPV infection, and viral hepatitis, evade
these immune responses and result in chronic infections. Several antiviral
drugs have been developed.

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The word is from the Latin neuter vīrus referring to poison and other noxious

liquids, from the same Indo-European base as Sanskrit visa, Avastin visa,
and ancient Greek ἰός (all meaning "poison"), first attested in English in 1398
in John Trevisa's translation of Bartholomeus Anglicus's De Proprietatibus
Rerum. Virulent, from Latin virulentus (poisonous), dates to c. 1400. A meaning of
"agent that causes infectious disease" is first recorded in 1728, long before the
discovery of viruses by Dmitri Ivanovsky in 1892. The
English plural is viruses (sometimes also Vira) whereas the Latin word is a mass
noun, which has no classically attested plural (Vira is used in Neo-Latin. The
adjective viral dates to 1948 The term virion (plural virions), which dates from
1959 is also used to refer to a single viral particle that is released from the cell and
is capable of infecting other cells of the same type.

There are 219 virus species that are known to be able to infect humans. The first
of these to be discovered was yellow fever virus in 1901, and three to four new
species are still being found every year. Extrapolation of the discovery curve
suggests that there is still a substantial pool of undiscovered human virus species,
although an apparent slow-down in the rate of discovery of species from different
families may indicate bounds to the potential range of diversity. More than two-
thirds of human viruses can also infect non-human hosts, mainly mammals, and
sometimes birds. Many specialists human viruses also have mammalian or avian
origins. Indeed, a substantial proportion of mammalian viruses may be capable of
crossing the species barrier into humans, although only around half of these are
capable of being transmitted by humans and around half again of transmitting
well enough to cause major outbreaks. A few possible predictors of species jumps
can be identified, including the use of phylogenetically conserved cell receptors. It
seems almost inevitable that new human viruses will continue to emerge, mainly

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from other mammals and birds, for the foreseeable future. For this reason, an
effective global surveillance system for novel viruses is needed.

Following on from the discovery of tobacco mosaic virus in 1892 and foot-and-
mouth disease virus in 1898, the first ‘filterable agent’ to be discovered in humans
was yellow fever virus in 1901.New species of human virus are still being
identified, at a rate of three or four per year (see below), and viruses make up
over two-thirds of all new human pathogens , a highly significant over-
representation given that most human pathogen species are bacteria, fungi or
helminths. These new viruses differ wildly in their importance, ranging from the
rare and mild illness due to Menangle virus to the devastating public health
impact of HIV-1.
In this paper, we take an ecological approach to studying the diversity of human
viruses (defined as viruses for which there is evidence of natural infection of
humans). First, we describe and analyse temporal, geographical and taxonomic
patterns in the discovery of human viruses . We then consider the processes by
which new human viruses emerge . There are a number of definitions of
‘emergence’ ; here, we are interested in all stages of the process by which a virus
shifts from not infecting humans at all to becoming a major human pathogen. As
experiences with HIV-1 and new variants of influenza A (and also with novel
animal pathogens such as canine parvovirus show, this shift can occur rapidly,
over time scales of decades, years or even months.
Of course, not all newly identified human virus species are ‘new’ in the sense that
they have only recently started to infect humans; many of them have been
present in humans for a considerable time but have only recently been
recognized. Moreover, we recognize that ‘species’ itself is an imprecise
designation, especially for viruses such as influenza A where different serotypes
can have very different epidemiologist and health impacts. Indeed, the
demarcation between genus, species complex, species, and serotype (or other
designations of sub-specific variation) can be somewhat arbitrary. Nonetheless, a
study of currently recognized ‘species’ is a natural starting point for attempts to
characterize and interpret patterns of virus diversity.

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As a starting point for our survey, we used a previously published database (see )
obtained by systematically searching the primary scientific literature up to and
including 2005 for reports of human infection with recognized virus species, using
species as defined by the International Committee on Taxonomy of Viruses
(ICTV) . The list of viruses was updated if either a new species that can infect
humans had been described in the literature and also recognized by the ICTV, if a
known species had been found in humans for the first time, or if there had been a
change in species classifications by the ICTV (notably for the human
papillomaviruses and the vesicular stomatitis viruses).

The year of discovery was taken to be the year of publication of the first report of
human infection. The place of discovery was determined from the original report
and recorded as the location of the diagnostic laboratory or, in the few instances
where this was not clear, the address of the first author of the report. We did not
attempt to locate the case itself, as this information was often lacking.

We obtained a list of 219 ICTV-recognized virus species that have been reported
to infect humans. 23 virus families were represented by species in this list.

The discovery curve is an ecological tool for estimating species diversity

comprising a simple plot of the cumulative number of species against time or
sampling effort. Discovery curves are normally drawn for defined geographical
areas; here we equate ‘humans’ with a delimited habitat for viruses. The
discovery curve for human virus species is shown in FIG

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As with all discovery curves, our curve reflects a number of different factors,
including: (i) the technology available for detecting viruses (ii) the effort invested
in detecting new viruses; (iii) the ‘visibility’ of different virus species, e.g. as a
function of how common they are and the nature of any disease caused; (iv) virus
taxonomy and the rules for designating a ‘species’; (v) the emergence of new
virus species that did not previously infect humans.

Numbers of species discovered by continent are shown in fig  (ignoring four

species for which the location of discovery could not be determined). That over

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60 per cent of species were first discovered in North America or Europe almost
certainly reflects considerable ascertainment bias . Rates of discovery by
continent have, perhaps unsurprisingly, been very variable through time but with
no clear patterns; the only notable trend in the last 15 years has been a higher
rate of discovery in Australasia.

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Numbers of species by family are shown in fig. The family containing the most
human virus species is the Bunyaviridae with 40; six families contain just one
human virus species. These numbers are too small for statistical analysis of rates
of discovery: the most notable trend is that only a single new pox virus has been
discovered since 1972 (compared with 10 up to that date). Nor are there any
striking patterns using other classifications such as RNA viruses versus DNA
viruses.

Following the approach described previously , we modelled human virus

discovery since 1954, assuming a total number of species available to be
discovered—the species pool—of N virus species, each discovered in any given
year with probability p. We considered fitting a distribution for values of p;
however, provided that the individual p values are low, there was minimal
improvement in model fit. The model was fitted to the data and evaluated using
Markov chain Monte Carlo (MCMC) methods with flat prior information to
calculate profile likelihood confidence intervals and the best fit parameters. The
model defines the expected number of discovered viruses in year t, λt, as
binomially distributed so that

2.1

where year t = 1 corresponds to 1954.

However, the binomial distribution B(N, p) can be accurately approximated by a

Poisson distribution with parameter Np for the range of values of N and p of
interest. Thus, for a set of model parameters, the likelihood of observing data X =
{xi}, the number of viruses discovered over years 1 to k, is given by

2.2

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We compared the model with the observed data by calculating the mean, trend in
the mean and variance for the number of virus species discovered per year (based
on 5 million simulations using best fit parameter values). The model reproduces
the observed data well: observed mean and variance 3.37 and 3.35, respectively;
fitted mean and variance 3.36 and 3.41, respectively. Parameter estimates,
however, are very uncertain owing to an unavoidable strong correlation
between N and pThe estimate of N is of particular interest: this has a central value
of 484 (i.e. 265 species remaining to be discovered), a lower 95% CI of 308 (89
remaining), an upper 90% CI > 2000 and an upper 95% CI that is undefined. Thus,
although there is considerable uncertainty as to the size of the human virus
species pool, this analysis suggests that there are at least dozens of new species
to be discovered, and possibly a very much larger number.

To make shorter term projections, the model was extrapolated to year 2020,
calculating 95% posterior prediction intervals using 2 million model simulations,
taking into account parameter uncertainty and model stochasticity. An upper limit
for N was set at the 90% upper confidence interval. This gave a projected number
of new virus species of 36 (95% CIs 20–57), corresponding to an average 2.4
species per year. This projection, of course, makes no allowance for any
improvements in virus detection technology nor changes in discovery effort.

Structure
Viruses display a wide diversity of shapes and sizes, called 'morphologies'. In
general, viruses are much smaller than bacteria. Most viruses that have been
studied have a diameter between 20 and 300 nanometers. Some filoviruses have
a total length of up to 1400 nm; their diameters are only about 80 nm. Most

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viruses cannot be seen with an optical microscope, so scanning and

transmission electron microscopes are used to visualise them. To increase the
contrast between viruses and the background, electron-dense "stains" are used.
These are solutions of salts of heavy metals, such as tungsten, that scatter the
electrons from regions covered with the stain. When virions are coated with stain
(positive staining), fine detail is obscured. Negative staining overcomes this
problem by staining the background only.

A complete virus particle, known as a virion, consists of nucleic acid surrounded

by a protective coat of protein called a capsid. These are formed from protein
subunits called capsomeres. Viruses can have a lipid "envelope" derived from the
host cell membrane. The capsid is made from proteins encoded by the
viral genome and its shape serves as the basis for morphological
distinction. Virally-coded protein subunits will self-assemble to form a capsid, in
general requiring the presence of the virus genome. Complex viruses code for
proteins that assist in the construction of their capsid. Proteins associated with
nucleic acid are known as nucleoproteins, and the association of viral capsid
proteins with viral nucleic acid is called a nucleocapsid. The capsid and entire virus
structure can be mechanically (physically) probed through atomic force
microscopy. In general, there are five main morphological virus types:

 Helical

These viruses are composed of a single type of capsomere stacked around a

central axis to form a helical structure, which may have a central cavity, or tube.
This arrangement results in virions which can be short and highly rigid rods, or
long and very flexible filaments. The genetic material (typically single-stranded
RNA, but single-stranded DNA in some cases) is bound into the protein helix by
interactions between the negatively charged nucleic acid and positive charges on
the protein. Overall, the length of a helical capsid is related to the length of the
nucleic acid contained within it, and the diameter is dependent on the size and
arrangement of capsomeres. The well-studied tobacco mosaic virus and

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inovirus  are examples of helical viruses.

 Icosahedral
Most animal viruses are icosahedral or near spherical with chiral icosahedral
symmetry. A regular icosahedron is the optimum way of forming a closed shell
from identical sub-units. The minimum number of capsomeres required for each
triangular face is 3, which gives 60 for the icosahedron. Many viruses, such as
rotavirus, have more than 60 capsomers and appear spherical but they retain this
symmetry. To achieve this, the capsomeres at the apices are surrounded by five
other capsomeres and are called pentons. Capsomeres on the triangular faces are
surrounded by six others and are called hexons. Hexons are in essence flat and
pentons, which form the 12 vertices, are curved. The same protein may act as the
subunit of both the pentamers and hexamers or they may be composed of
different proteins.

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 Prolate
This is an icosahedron elongated along the fivefold axis and is a
common arrangement of the heads of bacteriophages. This structure
is composed of a cylinder with a cap at either end.

 Enveloped
Some species of virus envelop themselves in a modified form of one of the cell
membranes, either the outer membrane surrounding an infected host cell or
internal membranes such as nuclear membrane or endoplasmic reticulum, thus
gaining an outer lipid bilayer known as a viral envelope. This membrane is
studded with proteins coded for by the viral genome and host genome; the lipid
membrane itself and any carbohydrates present originate entirely from the
host. Influenza virus, HIV (which causes AIDS), and severe acute respiratory
syndrome coronavirus 2 (which causes COVID-19)[84] use this strategy. Most
enveloped viruses are dependent on the envelope for their infectivity.

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 Complex
These viruses possess a capsid that is neither purely helical nor purely
icosahedral, and that may possess extra structures such as protein tails or a
complex outer wall. Some bacteriophages, such as Enterobacteria phage T4, have
a complex structure consisting of an icosahedral head bound to a helical tail,
which may have a hexagonal base plate with protruding protein tail fibres. This
tail structure acts like a molecular syringe, attaching to the bacterial host and then
injecting the viral genome into the cell.

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