To: jfcrow @ facstaff.wisc.edu (James Crow)

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Fcc: inbox

Subject: Mutagenesis as an invariant rate; HIV in germ

Dear Jim

I recognize there is a lot of empirical evidence to support

that invariance (pace exogenous mutagens), and a theoretical
framework how it¢ is balanced by evolutionary pressures. But the
more we learn about DNA metabolism, the less sense it makes
mechanistically. So let’s try the exercise of an open mind,

can we attribute changes in mutability to the physiological and
pathological context of the gametocytes? This is much in the
line of pheno-mutators that Ninio and others have been pushing.

    
 
 
 

"Why shouldn’t DNA repair be more or less accidentally contigent
on say virus infection, as well as toxic insults and direct

chemical attack on DNA? I don’t know of any direct measurement
of DNA repair efficiency as function of developmental stage, and
of miscellaneous pathologies.

 

 

I do come to believe that the germ line is remarkably well
insulated from run of the mill infectious agents; or is it just

lack of search? Gerry Weissman has passed on some references
on HIV entry into germ cells, but mainly mature gametes as far as
the asbtracts imply. (There has to be a route for retroviruses

to get in: there are so many integrated segments.)

Joshua.

Authors
Baccetti B. Benedetto A. Collodel G. di Caro A. Garbuglia AR.
Piomboni P.

Institution
Institute of General Biology, University and Center for the Study of
Germinal Cells, CNR, Siena, Italy.

Title
The debate on the presence of HIV-1 in human gametes. [Review] [48 refs]

Source
Journal of Reproductive Immunology. 41(1-2):41-67, 1998 Dec.

Abstract
The debate about the presence of HIV-1 particles in human gametes and
recent experimental results are reported in detail. Using
immunocytochemistry, in situ hybridization at electron microscopy level,
polymerase chain reaction and in vitro fertilization, it has been
demonstrated that human spermatozoa can incorporate HIV-1 using special
receptors, different from the usual CD4, and that they remain active and
able to vehicle the viral particles into the oocyte, which is regularly
fertilized. Moreover, by transmission electron microscopy (TEM),
immunocytochemistry and PCR, we demonstrated that cell-free HIV-1 is not
able to bind and penetrate the human oocyte in vitro. We attribute this
behaviour to the fact that the oocyte and cumulus cells are devoid both of
GalAAG and of CD4 receptors. PCR analysis indicated that mRNAs specific
for CD4, CXCR4 and CCRS proteins were absent, too. [References: 48]