dc.contributor.advisor | Morgenstern, Burkhard Prof. Dr. | de |
dc.contributor.advisor | Korber, Bette | de |
dc.contributor.advisor | Leitner, Thomas Dr. | de |
dc.contributor.author | Zhang, Ming | de |
dc.date.accessioned | 2012-05-16T12:09:18Z | de |
dc.date.available | 2013-01-30T23:50:51Z | de |
dc.date.issued | 2007-11-02 | de |
dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0006-B62A-5 | de |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-1312 | |
dc.description.abstract | In den letzten 26 Jahren konnte ein starker Anstieg
von HIV-1 auf globaler Ebene beobachtet werden. Die
außergewöhnliche Vielfalt von HIV-1 wird begründet
durch die hohe Mutationsrate, starke Replikation,
häufige Rekombination und strategische Verteilung von
N-linked glycosylation sites. In der
vorliegenden Arbeit wurde die genetische Variation von
HIV-1 mit besonderem Fokus auf der Rekombination und
den N-linked glycosylation sites untersucht. | de |
dc.format.mimetype | application/pdf | de |
dc.language.iso | eng | de |
dc.rights.uri | http://webdoc.sub.gwdg.de/diss/copyr_diss.html | de |
dc.title | Tracking HIV-1 genetic variation: recombination and N-linked glycosylation sites | de |
dc.type | doctoralThesis | de |
dc.title.translated | Analyse der Evolution von HIV-1 durch Subtyping und N-linked glycosylation sites | de |
dc.contributor.referee | Wingender, Edgar Prof. Dr. | de |
dc.date.examination | 2007-08-01 | de |
dc.subject.dnb | 500 Naturwissenschaften allgemein | de |
dc.description.abstracteng | The last 26 years saw a rampant global epidemic of
HIV-1. HIV-1 s extraordinary diversity is seeded by a
high mutation rate, rapid replication, frequent
recombination, and strategic placement and loss and
gain of N-linked glycosylation sites. In this thesis,
the genetic variation of HIV-1 was investigated with
special focus on recombination and N-linked
glycosylation sites.
Using phylogenetic analyses, distance methods, and
HIV-1 subtying tools including one called jumping
profile hidden Markov model, HIV-1 recombinants
dominating HIV epidemic in three different geographical
regions were examined. We found that CRF13_cpx includes
sections of the rare subtype J, and that breakpoint
inference can be greatly improved using all available
sequences within a CRF family. We confirmed that
CRF02_AG, a recombinant between subtype A and G that is
prevalent in West and West Central Africa, is an old
recombinant. The main recombination events that
generated CRF02 took place before the 1970 s, before
HIV-1 had started to spread worldwide and the currently
recognized subtypes had formed. Recombinants consisting
of subtypes B and C are frequently found in the HIV-1
epidemic of Asia, especially in southwest China where
they are associated with different drug trafficking
routes. Our study suggested that CRF07 was derived from
a recombination between CRF08 and subtype B. However,
it is possible that the currently defined CRF07 is not
the direct product of this recombination event. Lastly,
we found that recent recombination between subtypes B
and F in Argentina and Brazil, two epicenters in South
America, has created many different, but related,
recombinant forms. Taken together, it appears as if the
HIV-1 epidemic is becoming more complex as it moves
ahead into the future. Recombination among
co-circulating forms creates new forms of HIV-1 that
are now starting to dominate the epidemic in certain
parts of the world.
We developed methods to track N-linked glycosylation
sites (sequons) in HIV-1 as they shift positions and
vary in local densities. Comparing primate
lentiviruses, hepatitis C virus, and influenza A
viruses showed that generating and tolerating shifting
sequons is a unique evolutionary avenue for HIV-1
immune evasion. In addition, we found the primate
lentiviral lineages have host species - dependent
levels of sequon shifting, with HIV-1 in humans the
most extreme. Further, unlike influenza A hemagglutinin
H3 HA1 that accumulates sequons over time, HIV does not
have a net increase in the number of sites over time at
the population level, indicating that variation in
number and placement, not accumulation of N-linked
glycosylation sites, is more critical for HIV-1 immune
evasion.
The studies detailed in this thesis, together with our
great effort in re-subtyping > 150,000 sequences in
the Los Alamos HIV sequence database, enables us to
draw a more comprehensive and dynamic picture of the
global HIV-1 epidemic. | de |
dc.contributor.coReferee | Friedl, Thomas Prof. Dr. | de |
dc.contributor.thirdReferee | Waack, Stephan Prof. Dr. | de |
dc.subject.topic | Mathematics and Computer Science | de |
dc.subject.ger | Analyse der Evolution von HIV-1 durch Subtyping und Sequonanalyse | de |
dc.subject.eng | HIV-1 | de |
dc.subject.eng | genetic variation | de |
dc.subject.eng | recombinant | de |
dc.subject.eng | N-linked glycosylation sites | de |
dc.identifier.urn | urn:nbn:de:gbv:7-webdoc-1592-1 | de |
dc.identifier.purl | webdoc-1592 | de |
dc.affiliation.institute | Biologische Fakultät inkl. Psychologie | de |
dc.subject.gokfull | E | de |
dc.subject.gokfull | AH | de |
dc.subject.gokfull | W | de |
dc.identifier.ppn | 588952559 | de |