Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

XIV International AIDS Conference

Abstracts WePeA5740-WePeA5746 13

WePeA5740 The effect of oestrogen on human vaginal
susceptibility to HIV-1 infection
M. Li1, P.U. Cameron2, R.V. Short3. 'Pregnancy Research Centre, the
University of Melbourne, Pregnancy Research Centre, Royal Women's Hospital,
132 Grattan St., Carlton, Victoria 3053, Australia; 2Dept. of Microbiology and
Immunology, the University of Melbourne, Melbourne, Australia; 3Dept. of
Obstetrics and Gynaecology the University of Melbourne, Melbourne, Australia
Background: The human vaginal epithelium is well-supplied with HIV-1 receptive Langerhans cells, overlain by a stratified squamous epithelium. This epithelium is oestrogen-dependent, being thickest at around the time of ovulation, and
thinnest just before menstruation. Could oestrogen treatment be used to decrease
a woman's susceptibility to HIV-1 infection?
Methods: Vaginal biopsies were obtained from pre-and post-menopausal women
undergoing vaginal reconstructive surgery, with or without prior oestrogen replacement therapy The thickness of epithelium and the distribution of Langerhans
cells was assessed histologically and immunocytochemically.
Results: Preoperative oestrogen treatment increased the thickness of the vaginal
epithelium in post-menopausal women, but had no apparent effect on the number and distribution of Langerhans cells. Vaginal biopsies from pre-menopausal
women are currently being investigated.
Discussion: In all mammals, the vaginal epithelium is at its thickest, and is most
keratinised or cornified, at the time of the ovulatory peak of oestrogen secretion.
This may have evolved as a natural defence against sexually transmitted infections. Humans are the only species that frequently has intercourse other than at
the time of ovulation, perhaps making us particularly susceptible to STD's and
HIV-1 infection. Oestrogen treatment of ovariectomised Rhesus monkeys greatly
increases their resistance to vaginal SIV infection. We should therefore explore
the possibility that topical vaginal oestrogen treatment could increase a woman's
resistance to HIV-1 infection.
Presenting author: Mingjia Li, Pregnancy Research Centre, Royal Women's
Hospital, 132 Grattan St., Carlton, Victoria 3053, Australia, Tel.: [phone],
Fax: [phone], E-mail: [email protected]
WePeA5741 I Comparative changes in laboratory parameters of
Specified Pathogen Free (SPF) and non-Specified
Pathogen Free (non-SPF) laboratory cats infected
with Feline Immunodeficiency Virus (FIV)
J.H. Lamprecht', M.E. Austin2, M.W. Freestone3, P.J.D. Bouic4, A. Clark3,
W. Brittle3. 'Department of Pharmacology University of Stellenbosch, Cape
Town, South Africa; 2Central Research Unit, University of Stellenbosch, Cape
Town, South Africa; 3Essential Sterolin Products, 61 Clarendon Street, PAROW
VALLEY 7500, South Africa; 4Department of Medical Microbiology University of
Stellenbosch, Cape Town, South Africa
Background: Studies using non-SPF laboratory cats as a model for testing putative immune modulating drugs, were reported earlier. This study was performed
to determine if FIV+, SPF cats housed in a barrier unit would be a superior model.
Methods: A group of 8 purpose bred SPF cats housed in a barrier unit was infected with blood from a FIV+, SPF donor cat. Blood samples were taken weekly
for 6 weeks and then 6 weekly for 200 weeks. A similar group of 16 non-SPF
cats was used for comparison. Sero conversion was confirmed with an Elisa test.
Routine, standardised full blood count, differential white cell counts and lymphocyte subsets were recorded and plotted on the same graphs. Mean trend lines for
all parameters were compared and changes within groups and between groups
were statistically analysed using the SAS procedure for mixed models and a 5%
confidence interval.
Results: Large variations in individual as well as group means and medians were
noted in both groups. Many changes in and between groups reached statistical
significance, but were not clinically relevant. Highly significant and potentially clinically relevant differences between the groups were: Eosinophil count decreased
in the SPF group and increased in the non-SPF group. CD3 and CD8 percentage
decreased more rapidly in the non-SPF group. CD4 absolute count and CD4/CD8
ratio decreased more rapidly in the SPF group. Several cats in the non-SPF group
died during the study period, while none in the SPF group died.
Conclusions: Apart from a few selected parameters, the changes in standard
laboratory tests of FIV+, SPF and non-SPF cats are similar and the SPF model is
not superior. Differences can probably be explained by infective immune stimulation in the non-SPF cats. The use of a sophisticated and expensive SPF model in
long term studies using standard laboratory parameters is not essential. Survival
remains the most important parameter in non-SPF cats.
Presenting author: Johan Lamprecht, 61 Clarendon Street, PAROW VALLEY,
7500, South Africa, Tel.: [phone], Fax: [phone], E-mail: jhll
@sun.ac.za

WePeA5742 SHIV-KB9 infection of rhesus monkeys does not
always cause disease-Is it the host or the virus?
A.R Kourtis', C.I. Ibegbu2, F. Scinicariello3, Z.W. Chen4. 1Emory University,
3439 T N. Druid Hills Rd., Decatur GA 30033, USA, United States; 2Emory
Vaccine Center, Atlanta GA, United States; 3Emory University, Atlanta GA,
United States; 4Harvard Medical School, Boston MA, United States
Background: Simian-human immunodeficiency virus (SHIV) infection in the

macaque is a model of HIV pathogenesis. KB9, a molecular clone of SHIV 89.6P,
has been shown to be very virulent, inducing rapid and profound CD4+ T cell loss
in rhesus macaques, followed by partial recovery in some.
Methods: We intravenously inoculated 6 rhesus animals with the clone SHIV
KB9. All animals were housed at the Yerkes Primate Research Center. Immunophenotypic cell markers, specific antibody and cytokine production, viral
load, thymic output, and viral evolution were followed in the infected animals.
Results: We observed a previously not described clinical outcome of SHIV KB9
infection in 2 of 6 animals in our cohort. This consisted of lack of any signs of
immunodeficiency with sustained normal levels of CD4+ T cell counts, despite
viral loads that were comparable to those of the other 4 animals which exhibited
CD4+ T cell decline. The 2 animals displayed lower levels of CD8+ T cell activation during acute infection compared to the rest, and they preserved their thymic
output, as measured by the TREC assay, in contrast to the rest of the animals in
the cohort, whose thymic output rapidly decreased followed infection. However,
envelope-specific antibody production and avidity, and interferon-gamma production in response to stimulation with SIV and HIV antigens did not differ in the 2
animals compared with the other 4 animals in the cohort. The envelope V3-V5,
gp4l and the nef sequences remained identical in all infected animals.
Conclusions: KB9, even though a molecular clone, causes marked heterogeneity in clinical outcomes in the infected rhesus, including non-pathogenic infection.
Evolution of the viral clone in vivo does not appear responsible for this variability.
Host immune factors, and particularly thymic involvement, appear to be important
determinants of disease progression. These findings have further implications for
the use of this virus in vaccine studies.
Presenting author: Athena Kourtis, 3439 T N. Druid Hills Rd., Decatur GA
30033, USA, United States, Tel.: [phone], Fax: [phone], E-mail:
akourti @ pol.net
WePeA5743I Lack of breast-feeding transmission during
SIVmnd-1 primary infection in Mandrillus sphinx
I. Pandrea, R. Onanga 1, M. Makuwa, P. Rouquet 2, 0. Bourry2, P. Ngari1,
I. Bedjabaga, C. Apetreil, P. Roques'. ' Departement de Virologie, Centre
International de Recherches Medicales, Tulane Primate Center, Microbiology
Department, 18703 Three Rivers Road, Covington LA 70433, Gabon; 2Centre de
Primatologie, Centre International de Recherches Medicales, Franceville, Gabon
Background: SIVmnd-1 infects mandrills in natura. Mechanisms of virus persistence in wild population might include its vertical transmission, as reported in
CIRMF semi-free colony of mandrills. However, the mechanism(s) and timing of
transmission were not investigated to date. Here we present the first study of
SIVmnd-1 transmissibility by breast-feeding.
Methods: Six female mandrills were infected with mandrill plasma containing 300
TCID50 SIVmnd-1 the day afterthe delivery Blood was collected at days 0, 7, 10,
14, 21,28, 60, 90 and 180 p.i. from both mothers and offspring. Milk was collected
at the same sampling dates. Viral replication was investigated by measuring the
viral load (by in house RT-QC-PCR), the p26 antigenemia and the plasma RT.
Anti-SIVmnd-1 were detected by ELISA and WB and titered using SIVmnd-1 gp36
and V3 peptides. Lymphocyte subsets were determined: CD4/CD3, CD8/CD3,
CD4/CD8, CD4/CD28, CD8/CD28, CD4/HLA-DR, CD8/HLA-DR and CD20.
Results: Neither fever nor increase in the lymph node size was observed. Plasma
peak of viremia was observed by days 7-10 (2x106-4x108 RNA/ml), then decreased 10-1000 folds up to the levels found in chronic phase of naturally infected
mandrills. CD4+ cell counts and percentages decreased slightly during primary
infection (5-10%). CD8+ levels increased transiently. All values returned to that
recorded before infection without sign of CD8+ hyperactivation. Free virus was
present in the milk in concentrations of 4.7-5.6x1 05 RNA /ml. However, at the end
of the breast-feeding, after six months of follow-up, none of the offspring showed
virological evidences of SIVmnd-1 infection.
Conclusion: SIVmnd-1 replicated rapidly and extensively in mandrill mothers
but despite high levels of free virus in milk, no transmission occurred by breastfeeding. Alternative mechanisms (in utero or perinatal) should be investigated to
conclude the lack of vertical transmission of SIVmnd-1.
Presenting author: Ivona Pandrea, Tulane Primate Center, Microbiology Department, 18703 Three Rivers Road, Covington LA 70433, United States, Tel.: +1 985
871 6520, Fax: [phone], E-mail: [email protected]
WePeA5746 Engineered CD4/CXCR4-using simian
immunodeficiency virus from African Green
Monkeys is neutralization sensitive, replicates in
non-stimulated lymphocytes and induces
HIV-specific antibodies
R.R. Koenig, E. Flory, S. Steidl, J. Neumann. Paul-Ehrlich-Institut, Langen,
Germany
During human immunodeficiency virus type 1 (HIV-1) infection, disease progres
sion correlates with the occurrence of variants using the co-receptor CXCR4 for
cell entry In contrast, simian immunodeficiency virus from African green monkeys (SIVagm3mc), a non-pathogenic virus, uses CCR5, Bob and Bonzo as coreceptors throughout the course of infection. In this report, we studied the influence of an altered co-receptor usage on SIVagm3mc replication in vitro and in
vivo. Therefore the putative co-receptor binding domain, the V3 region of the surface envelope (SU) glycoprotein was replaced by the V3 loop of a CD4/CXCR4 -