Thursday, February 21, 2008

A Human Endogenous Retrovirus Reconstituted

Remember those HERVs we talked about in the previous post? A group from the Aaron Diamond AIDS Research Center at The Rockefeller University has reconstituted one of them using molecular techniques. The entire article is published in PLOS Pathogens, a free, full text, on-line journal.

These investigators have reconstitute a Class II HERV, HERV-K.
A pseudo-ancestral HERV-K DNA sequence was synthesized and used to produce viral proteins and RNA that could reconstitute the HERV-K replication cycle. Thus, the replication and biology of a once-extinct retrovirus can now be studied in the laboratory. Interestingly, reconstituted HERV-K replication experiments, and comparison of the reconstituted HERV-K DNA sequence with the dead HERV-Ks in modern human DNA, suggests that HERV-K may have been extinguished in humans in part by host defenses that induce mutation of retroviral DNA and that the reconstitution of the pseudo-ancestral HERV-K reversed these changes.
This further suggests that infection with ancient retroviruses induced selective pressure on the human immune system allowing us to resist infection with certain retroviruses.
Two major components of intrinsic defense against retrovirus and retroelement replication in primate cells are the TRIM5 and APOBEC3 gene products [40–42]. Analysis of these genes in modern primates indicates that these genes have likely been under positive selection pressure for significant portions of primate evolution [12–16]. As an endogenous retrovirus that has also apparently replicated exogenously and has been active for much of Old World primate evolutionary history, HERV-K is an excellent candidate for an agent that has imposed sustained evolutionary pressure on antiretroviral defenses present in modern primates.
The Introduction and Discussion in this article is very readable. Give it a try.

Human Endogenous Retroviruses

I'm adding this post before I forget about it. We will discuss it more when we cover viruses.

Human Endogenous Retroviruses. These pieces of DNA are 'fossil's of retroviruses that were incorporated into the human germline DNA over thousands to hundreds of thousands to millions of years. They make up about 1% of the human genome. The first HERV was identified in 1981. So far, at least 20 HERV families have been identified (find free text article by M. Tristem here). There are lots of things cool about HERVs. First, they may be involved in the pathogenesis of some diseases, such as cancer, Sjogren's syndrome, Rheumatoid arthritis, Multiple sclerosis or Systemic Lupus Erythematosus, to name a few.

HERVs have been classified into 3 groups based on sequence identity with animal retroviruses.

Class I HERVs share sequence homology with infectious mammalian type C viruses. Examples would be porcine endogenous retrovirus, murine leukemia virus and baboon endogenous virus.

Class II HERVs share sequence homology to mammalian type A, B and D related retroviruses. HERV-K is a member of this group and is one of the most active HERVs. HERV-K can actually form virus-like particles.

Class III HERVs are foamy virus related HERVs and include only HERV-L. This is the oldest known genus of Retroviridae and more can be found about them here.

Why have HERVs been so successfully maintained in our genome? This person has one hypothesis. Is is possible that HERV's somehow serve the needs of the host? Also here.

Science fiction novelist Greg Bear has a series of novels in which HERV's play an important role in evolution.

Tuesday, February 19, 2008

Teratoma

A teratoma is a tumor derived from pluripotent stem cells. The word teratoma is from the Greek meaning monstrous tumor. Teratomas are derived from germ cells, sperm and ova and thus can form tissue from endoderm, mesoderm and ectoderm. Thus these tumors can contain hair, bone and even teeth. Rarely, a more developed organ such as an eyeball or hand can be formed. Some forms of teratomas, Fetus in fetu and fetiform teratoma, can even resemble a malformed fetus. Pictures of these types of teratomas can be found here and can be quite shocking.

Here is a link to ovarian teratomas. There are two different kinds of ovarian teratomas. Mature teratomas which are benign and immature teratomas that are cancerous. A short review on teratomas can also be found here.

Pressure Ulcers


There is a worthwhile article on pressure ulcers (bedsores) in todays New York Times Science section. An excellent review of this condition can be found at massage therapy. More information can be found here and here.