
Research at
the Center for Molecular Medicine and Genetics on
MUCOSAL TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
(HIV-1)
Focused on the Long Terminal Repeat (LTR)
Hosted by Anton Scott
Goustin,
Ph.D., and Robert A.
Thomas, Ph.D. Center for
Molecular Medicine and Genetics, Wayne State University, Detroit,
Michigan USA
"The more we know about the AIDS epidemic, the worse it appears
to be," said Dr Peter Piot, Executive Director of UNAIDS. "We
are now realizing that rates of HIV transmission have been grossly
underestimated - particularly in sub-Saharan Africa, where the
bulk of infections have been concentrated to date. South Africa
now estimates that one in 10 adults are living with HIV - up by
more than a third since 1996. And in Namibia, AIDS now kills
nearly twice as many people as malaria, the next most common killer."
You can read more here
Heterosexual transmission is the predominant mode of transmission
worldwide, according to a recent article in The
Lancet:
"Sexual transmission is by far the most important, accounting
for over 75% of all HIV infections
world wide. During the early phases of the epidemic, homosexual
transmission was the
predominant mode in developed countries. However, during the past 5 years,
there has been
evidence of increasing trends for heterosexual transmission in
industrialised countries. In
the Caribbean, heterosexual transmission has now replaced homosexual
transmission as the
major mode of HIV spread."
Molecular epidemiology: the HIV-1 subtypes:
- At least nine HIV-1 subtypes (A, B, C, D, E, F, G, H and O) occur on
the African
continent
- Importance of understanding HIV-1 subtypes and HIV-1
genetic diversity in order to vaccinate throughout Africa
- The wonderful HIV sequence
database maintained at Los Alamos National Labs in New Mexico, USA by
Gerald Myers and Bette Korber
- The JAMA article on HIV-1 diversity:
Hu DJ, Dondero TJ, Rayfield MA< George JR, Schochetman G,
Jaffe HW, Luo C-C, Kalish ML, Weniger BG, Paul C-P, Schable CA, Curran JW.
(1996). The emerging genetic diversity of HIV: the importance global
surveillance for diagnostics, research, and prevention. J. Amer. Med.
Assoc. (Jan 17, 1996)).
- Subtype C, even beginning to creep into
the USA.
This subtype is present now on five continents and in 21 nations,
most recently including Malaysia (Brown et al., AIDS Res. Human
Retrov. 12(17), 1655-1657.
- Our group is studying subtype-specific differences in the regulation
of HIV-1 gene expression:
Zachar V, Thomas RA, Zacharova V, Ebbesen P, Goustin AS. (1994). Basal
and Tat-transactivated expression from the human immunodeficiency
virus-1 long terminal repeat in human placental trophoblast rules out
promoter-enhancer activation as the partial block to viral
replication.
J. Gen. Virology. 75(6), 1461-1468.
and
Zacharova V, Becker MLB, Zachar V, Ebbesen P, Goustin AS. (1997). DNA
sequence analysis of the long terminal repeat of the C subtype of
human immunodeficiency virus type 1 from southern Africa reveals
a dichotomy between B subtype and African subtypes on the basis
of upstream NF-IL6 motif.
AIDS Research & Human Retroviruses 13(8), 719-724.
A paper focused
on the function of the diverse elements in the
C and E
subtype viruses appeared recently in J. Virol. from Max Essex' group at
the Harvard AIDS Institute:
Montano MA, Novitsky VA, Blackard JT, Cho NL, Katzenstein DA, Essex M.
(1997). Divergent transcriptional regulation among expanding human
immunodeficiency type 1 subtypes.
J. Virol. 71(11), 8657-8665.
Other issues in maternal-fetal transmission
Zachar V, Hager H, Koppelhus U, Zacharova V, Liu X, Bambra C, Goustin AS,
and Ebbesen P. (1997). Elevated IFN-alpha in maternal and umbilical
cord
blood, and in the placental trophoblast suggests natural protection
against vertical transmission of HIV-1 in a Kenyan cohort.
AIDS
[London]
11, 383-384.
Zacharova V, Zachar V, Goustin AS. (1997). Sequence of chemokine reeptor
gene CCR5 in chimpanzees, a natural HIV-1
host.
AIDS Res. Hum.
Retroviruses, accepted for publication, slated for August 20, 1997 issue.
In this paper, we report the sequence of the chemokine receptor CCR5
in
chimpanzees, a species which can be infected by HIV-1, but does not
succumb to HIV pathogenesis (AIDS) for reasons which are completely
opaque. Chimp CCR5 differs from human CCR5 at two positions, N13D and
X130X. David Kabat's group at the Oregon Health Sciences University,
however, has recently reported (J Virol 1997 Nov;71(11):8642-865) that
substitution of TYR by ASN at the 14
position (as found in the African green monkey CCR5) ablates the ability
of AGM CCR5 to serve as a receptor for macrophage-tropic strains of HIV-1.
It is not known whether substitution of ASP (D) for ASN (N) at the 13
position has a similar effect on the ability of chimp CCR5 to serve as a
receptor for m-tropic HIV-1.