HTML virology...

[RYBICKI, ED]

Dear colleagues:

Inspired by the wonderful workings of the World-Wide Web - and the 
excellent virology site, which I can reach now and then - I have 
been dabbling in the weirdnesses of an HTML editor in order to 
construct a virology "hypertext", based loosely on what I teach 
second-year-undergraduates.  That is to say, introductory 
molecular-based virology concentrating on replication mechanisms.  
Right now I am using Cello as a hypertext browser; I would like to 
use Mosaic, but one has to configure it with a null Winsock.dll on 
my system to stop it looking frantically for servers outside the 
home computer.  Of course, like any project of this sort, it has got 
away from me, and is assuming the proportions of a textbook as the 
HTML files multiply like rabbits and the illustrations become more 
and more lurid and larger and larger.

Is anyone else interested in such a thing?  Should I attempt to zip 
it up and dump it to Jean-Yves' ftp site (being as it would tax your 
patience to ftp it from our site, given slowness of phone lines to 
here)?  Please email with the odd comment (or even ordinary ones), 
and I would like to know if anyone else (eg. Cris Woolston) has done 
anything similar, and if the possibility exists to swap modules, 
etc.  We could potentially get quite a body of teachable, up-to-date 
virology this way - that is, by experts writing expert modules, 
and swapping them - and it would be wide-based as presumably it 
doesn't matter what platform you use, as the relevant files are all 
ASCII text anyway, and formatted by your browser.

I welcome suggestions/comments.  I attach an excerpt from my basic 
text FYI and for test purposes.

Cut here:
____________________________________________________________________
<H1>An Introduction To Virology</H1>

<P>
<H2>An Introduction To Virology</H2>
<P>
<H3>What is a Virus?</H3>
<P>
Viruses have been defined as:<P><H3>"...entities whose genomes are 
elements of nucleic acid that replicate inside living cells using 
the cellular synthetic machinery, and cause the synthesis of speci
alised elements [virions] that can <A HREF = "#virus">transfer the 
genome to other cells"</A></H3>. <P> The <A NAME = 
"concept">concept</A> of a virus as an organism challenges the way 
we <A HREF = "
#organisms">define life:</A><A NAME = "viruses"> viruses</A> do not 
respire, nor do they display irritability; they do not move and nor 
do they grow, however, they do most certainly reproduce, and ma
y adapt to new hosts.  By older, more zoologically and botanically 
biased criteria, then, viruses are not living.  However, this sort 
of argument results from a "top down" sort of definition, which h
as been modified over years to take account of smaller and smaller 
things (with fewer and fewer legs, or leaves), until it has met the 
ultimate "molechisms" or "organules" - that is to say, viruses -
 and has proved inadequate.

If one defines life from the bottom up - that is, from the simplest 
forms capable of displaying the most essential attributes of a 
living thing - one very quickly realises that the only real criterio
n for life is:

<H2>The ability to replicate</H2>


and that only systems that contain nucleic acids - in the <A HREF = 
"#computer viruses">natural world</A>, at least - are capable of 
this<A NAME = "phenom"> phenomenon</A>.  This sort of reasoning ha
s led to a new definition of <A HREF = "#organism">organisms:</A>
<P>
<P><H2>"An organism is the unit element of a continuous lineage with 
an individual evolutionary <A NAME = "history">history</A>"</H2>.
<P>
<P>
The key words here are UNIT ELEMENT, and INDIVIDUAL: the thing that 
you see, now, as an organism is merely the current slice in a 
continuous lineage; the individual evolutionary history denotes the 
independence of the organism over time.  Thus, mitochondria and 
chloroplasts and nuclei and chromosomes are not organisms, in that 
together they constitute a continuous lineage, but separately have 
no
 possibility of survival, despite their independence before they 
entered <A HREF = "#margulis">initially symbiotic</A>, and then 
dependent <A NAME = "dependent">associations</A>.  The concept of 
repl
ication is contained within the concepts of a continuous lineage, 
and an evolutionary history.  Thus, given this sort of lateral 
thinking, viruses become quite respectable as organisms: they most 
def
initely replicate, their evolution can (within limits) be traced 
quite effectively, and they are independent in terms of not being 
limited to a single organism as host, or even necessarily to a singl
e species, genus or phylum of host.
<P><P>
<H3>Origins of Viruses</H3><P>
The probably multiple origins of viruses are lost in a sea of 
conjecture and speculation, which results mostly from their nature: 
no-one has ever detected a fossil virus as a particle; they are too 
s
mall and probably too fragile to have withstood the kinds of 
processes that led to fossilisation, or even to preservation of 
short stretches of nucleic acid sequences in leaf tissues or insects 
in <A
 HREF = "#fossil">amber</A>.  <A NAME = "result">As a result</A>, we 
are limited to studying viruses that are isolated in the present, or 
from material that is at most a few decades old.  The new sci
ence (or art) of <A HREF = "#taxon">virus molecular systematics</A> 
is,<A NAME = "however"> however</A>, shedding a great deal of light 
on the distant relationships of, and in some cases on the presu
med origins of, many important groups of viruses.  For example, <A 
HREF = "#picorna">picornaviruses</A> of mammals are very similar 
structurally and genetically to a large number of small RNA viruses
 of insects and to at least two plant viruses, and - as the insect 
viruses are more diverse than the mammalian viruses - probably had 
their origin in some insect that adapted to feed on mammals at so
me point in evolutionary time.  Picornaviruses also have a very 
similar genomic organisation to  <A HREF = "#como">comoviruses</A> - 
despite the latter having two genomic components instead of one - 
and can feasibly proposed to be evolutionarily related to 
comoviruses, albeit distantly.  Still more distant is a relationship 
with <A HREF = "#poty">potyviruses</A>: these share only a "core" 
replic
ase-related sequence, and have <A HREF = "poty.gif">filamentous</A> 
particles rather than <A HREF = "picorna.gif">spherical</A>.  A case 
can be made for descent from a single ancestor of at least the
 replicase-aasociated functions of all viruses with positive-sense 
and negative-sense single-strand <A HREF = #"RNA virus">genomes</A>; 
likewise, large DNA viruses like pox- and herpes viruses could 
be presumed to have <A HREF = "#taxon">"degenerated"</A> (if one 
believes<A NAME = "degen return"> viruses</A> to be degenerate 
organisms, which I for one do not...) from cellular organisms, given 
th
at their enzymes share more sequence similarity with sequences from 
cells than with other viruses or anything else.  <A HREF = 
retro>Retroviruses, pararetroviruses, retrotransposons and 
retroposons</
A> all probably share a common origin of the reverse transcription 
function, which in turn may be a living relic of the enzyme that 
enabled the switch from a presumably <A HREF = "#RNA world">RNA-bas
ed genetics</A> to DNA-based heredity. 

<P><P> Whatever the implications of sequence relationship studies, 
it is very quickly apparent that viruses as a class of organisms are 
polyphyletic: that is, they have more than one origin.  What th
ey have in common is a role as the ultimate "stripped-down" 
parasites: organsisms which can only undergo a life cycle inside the 
cells of a host organism, using at the very least the metabolic 
enzyme
s and pathways and ribosomes of that host to produce virion 
components which get assembled into infectious particles.<P><P>

<H3>Genome Diversity and Genomic Replication Strategies</H3><P>
Viruses are the only organisms on this planet to still have RNA as 
their sole genetic material.  They are also the only autonomously 
replicating organisms to have single-stranded DNA.  The range of v
irus genomes as found in virions encompasses single-component dsDNA, 
linear or circular (occasionally circularly permuted linear); 
single, double or multi-component circular ssDNA; single-component l
inear ssDNA; single or multi-component dsRNA; single or multiple 
component ssRNA genomes which may be totally "positive"(or 
messenger) polarity, totally "negative" (or anti-messenger) 
polarity, or pa
rtially positive negative-sense; "diploid" positive-sense ssRNA 
genomes which replicate via reverse transcription to and 
trascription from longer-than-genome-length dsDNA, and nicked and/or 
partially
 dsDNAs which replicate via transcription to and  reverse 
transcription from longer-than-genome-length positive-sense ssRNA.  
In contrast, prokaryotes have only single-component circular 
(mainly) or 
linear (Streptomyces) dsDNA while all eukaryotes have 
multi-component dsDNA, and all the genomes replicate via the classic 
semi-conservative route.

These various types of virus genomes can be broken down into seven 
fundamentally different  groups, which obviously require different 
basic strategies for their replication.  David Baltimore, who ori
ginated the scheme, has given his name to the so-called <A HREF = 
"genomes.htm#baltimore">"Baltimore Classification"</A> of virus 
genomes.




<P><P><P><P><P><P><P><P>
<A NAME = "organisms"><H2>Classical Properties of Living 
Organisms:</H2></A>
<P><UL>
<LI>Reproduction
<LI>Nutrition
<LI>Irritability
<LI>Movement
<LI>Growth
</UL>
<P>
<A HREF = "#viruses">(return)</A>
<P><P><P><P><P><P><P><P>

<A NAME = "virus"><H2>Definition of a Virus:</H2></A>
<P>SE Luria, JE Darnell, D Baltimore and A Campbell (1978).  General 
Virology, 3rd Edn.  John Wiley & Sons, New York, p2 of 578.
<A HREF = "#concept">(return)</A>
<P><P><P><P><P><P><P><P>
<A NAME = "organism"><H2>Definition of an Organism:</H2></A>
<P>SE Luria, JE Darnell, D Baltimore and A Campbell (1978).  General 
Virology, 3rd Edn.  John Wiley & Sons, New York, p4 of 578.
<P><A HREF = "#history">(return)</A>
<P><P><P><P><P><P><P><P>


<A NAME = "computer viruses"><H2>Computer Viruses as Life 
Forms:</H2></A>
<P>Steven Hawking, of black holes fame, apparently believes that 
computer viruses should count as life: they are obligate parasites 
which exploit the "metabolism" of the host computer they infect, th
ey replicate in the form of their source code [=genome], and they 
newest and nastiest can mutate while they do so (Weekend Argus, 6-7 
August, 1994).
<P><A HREF = "#phenom">(return)</A>
<P><P><P><P><P><P><P><P><P><P><P><P><P><P><P><P>
<A NAME = "fossil"><H2>Fossil DNA:</H2></A><P>
Short stretches of DNA - no more than 500 nucleotides - have been 
amplified up<I> in vitro</I> by the technique of polymerase chain 
reaction or PCR, from mites entombed in amber up to 200 MYr BP, and
 from fossilised leaves up to 60 MYr old.  This DNA can be sequenced 
and compared to that of morphologically related modern organisms.
<P><A HREF = "#result">(return)</A>
<P><P><P><P><P><P><P><P><P><P><P><P><P><P><P><P>

<A NAME = "taxon"><H2>Virus Taxonomy Reference:</H2></A>
<P>FA Murphy and DW Kingsbury (1990).  Virus Taxonomy.  Chapter 2 in 
Fields Virology, 2nd. Edn. (BN Fields et al, Eds.)  Raven Press, New 
York.
<P>EG Strauss, JH Strauss and AJ Levine (1990).  Virus Evolution.  
Chapter 9 in Fields Virology, 2nd. Edn. (BN Fields et al, Eds.)  
Raven Press, New York.
<P><A HREF = "#however">(return 1)</A>
<P><A HREF = "#degen return">(return 2)</A>
<P><P><P><P><P><P><P><P><P><P><P><P><P><P><P>
<A NAME = "margulis"><H2>Origin of Eukarya:</H2></A>
<P>Eukarya probably arose from cells which probably most closely 
resembled Archaea-like organisms (Archaebacteria), about 1.4 billion 
years ago.  Their key differences from Prokarya and Archaea - the
 possession of nuclear membranes and mitochondria - are difficult to 
explain.  The former may be a simple adaptation to localise 
functions specific to DNA replication and transcription, and may 
have 
happened independently in at least one other of the Bacteria.  The 
latter, however, is postulated to have had its origins in an 
endosymbiotic association of a free-living bacterium with another 
with 
aerobic respiration, possibly related to the present-day 
<I>Agrobacterium, Rhizobium and Rickettsias</I>: the latter would 
have been present in the cytoplasm of the former, and would 
gradually have l
ost its cell wall (though remaining enveloped), and much of its 
genome (much of whose function was taken over by the host), though 
retaining its own DNA replication, circular genome structure, and ri
bosomal RNA and protein genes.  This would have been the origin of 
true Eukarya, all of whom would descend from this pioneering 
symbiosis.

Another endosymbiosis which became permanent happened at least once 
(and possibly several times) much later on in evolution, with the 
entry into symbiosis of a primitive member of the Eukarya and a p
hotosynthetic bacterium: this was possibly an ancestral relative of 
<I>Prochloron</I>, which has similar chlorophyll, but may have been 
a cyano- (blue-green)bacterium.  As happened with mitochondria,
 the chloropast percursor lost its wall, and much of its genome; 
however, as it occurred much more recently in evolutionary time, 
chloroplast genomes are usually much larger than mitochondrial 
genome
s.  Several eukaryotic marine algae have chloroplasts which appear 
to have different origins than those of all land plants: these may 
have been independent acquisitions.  Still others have complicate
d multi-membrane layered chloroplasts which appear to have vestigial 
nuclei: these are probably derived from primitive photosynthetic 
eukaryotes which formed endosymbiotic associations with other euk
aryotes.

<H3>Reference</H3>: Prescott et al., Microbiology: 2nd. Edn.
<P><A HREF = "#dependent">(return)</>
<P><P><P><P><P><P><P><P><P><P><P><P><P><P><P>


  _________________________________________________________________
 | Ed Rybicki, PhD          |         Well, I tip my hat           |
 | (ed at micro.uct.ac.za)     |      To the new constitution         |
 | Dept Microbiology        | Take a bow for the new revolution... |
 | University of Cape Town  |  Then I get on my knees and pray     |
 | Private Bag, Rondebosch  |   We don't get get fooled again...   |
 | 7700, South Africa       |                                      |
 | fax: xx27-21-650 4023    |      - Pete Townshend, 1972          |
 | tel: xx27-21-650 3265    |      (Won't get fooled again)        |
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