Identification and Characterization of Gorilla Specific HERV-K (HML-2) Endogenous Retroviruses
Holloway, Joseph.
2019
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HERV-K (HML-2) is the
most recently active endogenous retrovirus group in humans, and the only group with
human specific proviruses. Some of these proviruses are insertionally polymorphic and
contain intact open reading frames, providing evidence of recent activity. HML-2
proviruses are also found throughout the Catarrhine primates. Although these proviruses
seem to be functionally extinct in ... read moreboth humans and chimpanzees, less is known about the
HML-2 profile and activity of proviruses in gorillas. The present work aimed to identify
and characterize novel HERV-K (HML 2) elements in the gorilla genome to provide a more
complete view of the group, assess their activity during the evolution of closely
related primate species, and investigate their potential for current infectious
activity. Gorilla specific HML-2 proviruses were identified through targeted PCR site
amplification and deep sequencing using a modified integration site assay, by mining
data from the Great Ape Genome Project, and by filtering the gorGor5 reference genome.
Our investigation led to the identification and characterization of 31 gorilla specific
2-LTR proviruses. Most of the proviruses are insertionally polymorphic and appear to
have integrated very recently. A PCR screen of the loci across ten separate gorilla
samples revealed that over half were present in less than 50% of the samples, and 9
found in only one sample. Consistent with their recent origin, many contain one or more
full length open reading frames, with one provirus displaying full length open reading
frames for all retroviral genes. The profile of these HML-2 proviruses suggests that
they were active more recently than those found in humans or chimpanzees. To investigate
the relationship further, phylogenetic analyses were conducted. A neighbor-joining LTR
phylogeny of species-specific sequences shows the division into three distinct clades,
with the gorilla LTR sequences representing some of the youngest sequences, <300,000
years, based on mutational divergence. To better estimate the time of integration,
molecular clock analysis was done using a nearest LTR node approach, which placed the
average integration time of the youngest group of gorilla specific integrations at ~0.9
MY. These data taken together lead to the possibility that HML-2 has been active much
more recently in gorillas than in humans. We suggest that gorillas may still harbor
infectious HML-2 virus, and could serve as a model for understanding retrovirus
evolution and pathogenesis in humans.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Pharmacology & Experimental Therapeutics.
Advisor: John Coffin.
Committee: Theoharis Theoharides, John Castellot, and Naomi Rosenberg.
Keywords: Virology, and Evolution & development.read less - ID:
- br86bg51m
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