Ian A. York (york at mbcrr.dfci.harvard.edu) wrote:
: In article <Cy5G7t.It5 at eecs.nwu.edu> markb at hook.eecs.nwu.edu (Mark E. Brodsky) writes:
: >Thank you. Others have written me saying that retroviruses have two
: >copies of their genome, such is the case with HIV for instance. Does
: >anyone know why this is? I thought viruses were supposed to be models
: >of efficiency. Aren't two copies of the same genome wasteful if the
: >organism doesn't reproduce sexually?
: "Models of efficiency"? I think not. In many viruses (at least all that
: I have worked with) the output from an infected cell consists mostly of
: noninfective particles - frequencies range from 10:1 for some HSV up to
: 1000's:1. These particles may be able to enter a cell and even to
: initiate a round of replication, but are not able to complete infection to
: form new particles. In many viruses, you can get DI (defective
: interfering) particles, which actively inhibit replication of "real"
: particles. Although there are many arguments as to the function of these
: things, it seems plausible to me that there is no function. Viruses do
: use their genome with tremendous efficiency (look at the number of
: proteins an adenovirus genome can express) but they are too small to
: build in clean regulatory functions. In many cases their best strategy
: might be replicate like hell, and hope that their will be enough good
: stuff in the output to keep going.
: Of course, while this is a general statement, it doesn't address
: the retrovirus two-genomes situation, which sounds more like a feature
: than a bug. Could that be a redundancy to hopefully overcome possible
: defects in one of the genomes?.
Yes, many of the viruses produce lots of noninfectious particles and are
in this respect not particularly effective. On the other hand, it isn't
very important for them to be so energy-efficient, parasites as they are.
They also usually do not compete with other viruses, a setting in which
the more efficient would prevail; their battle is mainly with their host.
Like many other parasites they make a very large number of offspring,
each of them having a rather low probability of success. Viruses sure
could reproduce faithfully if it was vary important for them, it
just isn't. Ensuring genetic variation, e.g. to escape the immune
response is more urgent.
For the retroviruses. it is interesting to note that the misincorporation
rate of the reverse transcriptase seems to be about one error per 10 000
nucleotides - about the size of their genome. A sustantial proportion of
offspring will differ in sequence from the parent genome. This may be
seen as a *deliberate* mechanism to ensure variation, but we must also
keep in mind that half of the retroviral genome replication,
transcription from the proviral DNA, is performed by RNA pol II, which
probably hasn't very high fidelity itself. There thus is no point for the
virus to make a more faithful reverse trancriptase.
As to the use of the two genome copies, it looks like the first template
switch in reverse transcription may occur from one copy to the other,
whereas the second transfer seems to be intramolecular. This could be
the result if the first transfer happens in crowded conditions within
the incoming capsid and the second after disassembly. See Hu and Temin
(1990), PNAS 87, 1556-60. It is theoretically possible that both
copies give rise to complete provirus DNAs, being able to complement
each other's defects. It looks, however, like the more usual situation
is that one virion gives rise to only one integrated provirus.
Rearrangements and homologous recombination in retroviruses is quite
common. The frequency of recombination is so high that two sites 1 kb
apart is reported to segregate independently.
Olav Hungnes olav.hungnes at embnet.uio.no
National Institute Phone (+47)22042200
of Public Health FAX (+47)22353605