Alain J. Georges

Evidence in Gabon for an intrafamilial clustering with mother‐to‐child and sexual transmission of a new molecular variant of human T‐lymphotropic virus type‐II subtype B

Following the observation of an HTLV‐II seropositive 60‐year‐old woman living in Gabon (Central Africa), a serologic and molecular study of her family members was conducted in an attempt to determine the duration of the HTLV‐II infection and the modes of transmission of the virus. Among 41 family members, five were HTLV‐I seropositive and 7 exhibited specific HTLV‐II antibodies in their sera as demonstrated by high immunofluorescence titers on C19 cells and/or specific Western‐blot pattern. The second husband of the index case and two of his sisters were infected by the virus, suggesting the presence of HTLV‐II in this family over two generations. Sequence analysis of an amplified fragment of 172 nucleotides within the gp21 of the env region (6469–6640) of four HTLV‐II infected individuals revealed a new HTLV‐II molecular variant of the subtype b diverging from the prototypes NRA and G12 by seven (4.1%) and five (2.9%) bases substitutions, respectively. Molecular analysis of the total env gene (1462 bp) and fragments of the pol and pX regions confirmed that this new African variant was the most divergent HTLV‐II subtype b yet described, exhibiting 2.3% of nucleotide substitutions in the env gene (33 bases) as compared to the two HTLV‐II b prototypes. These data demonstrate, for the first time in Africa, intrafamilial both mother‐to‐child transmission and sexual transmission between spouses of an HTLV‐II b molecular variant, and also suggest that this virus has been present in Gabon for a long period of time.

Protection of cynomolgus macaque against cervicovaginal transmission of SIVmac251 by the spermicide benzalkonium chloride.

Summary: We evaluated the potential effectiveness of a spermicide cationic surfactant, benzalkonium chloride (BZK), to prevent the transmission of simian immunodeficiency virus (SIV) after intravaginal inoculation in 12 cynomolgus macaques. The inoculation procedure involved deposition of 6.7 ivag‐AID50 of cell‐free SIVmac251 into the receiving vagina, four times over a 2‐week period, at the end of the luteal phase of the menstrual cycle. Six randomly selected females received vaginally foam containing BZK (7.37%, wt/wt) before each inoculation (BZK group), whereas the remaining were not pretreated (control group). In controls, 5 animals presented persistent SIV infection and 1 had a transient viremia. The number of uninfected animals was higher in the BZK group (6 of 6) than in controls (0 of 6). These findings demonstrate that BZK placed in the vaginal receptacle prior to SIV inoculation provides a significant protection in vivo. The wide spectrum of antimicrobial activities of BZK (including HIV) in addition to its efficiency to block the transmucosal passage of SIV in the macaque model qualifies this drug as an attractive topical microbicide to prevent sexually transmitted infections in humans.

Low prevalence of neuro-psychiatric clinical manifestations in central African patients with acquired immune deficiency syndrome.

In order to evaluate the frequency of neurological and psychiatric disorders in central African patients with acquired immune deficiency syndrome (AIDS), 93 inpatients at the National Hospital Centre of Bangui were selected according to the World Health Organization (Bangui) clinical definition of AIDS and were confirmed to be serologically positive for human immunodeficiency virus (HIV) 1 (92/93) or HIV 2 (1/93) by Western blot. Neurological (11/15) and psychiatric (4/15) abnormalities were clinically detected in 16% (15/93) of African patients with AIDS. In this series, the prevalence of neuro-psychiatric disorders appeared to be lower than in Europe and North America.

IgG4 serology of loiasis in three villages in an endemic area of south-eastern Gabon

Human filariasis due to Loa loa differs from other filariasis in that the majority of infected subjects are without circulating microfilariae (occult loiasis). In search for alternative diagnostic methods, which do not depend on circulating microfilariae or the (rather infrequent) eye‐passage of adult worms, it was shown earlier that IgG4 antibodies directed against Loa loa adult worm antigen are apparently a good marker of occult loiasis and specific with regard to the sympatrically occurring Mansonella perstans. In this study we evaluated an IgG4 antibody‐based ELISA using crude extract of Loa loa microfilariae (which is easier to obtain than adult worm) to estimate the prevalence of loiasis in 3 villages in South‐East Gabon. Of 222 examined individuals (80 children < 16 years, 142 adults) 44 (20%) carried Loa loa microfilariae and 170 (77%) M. perstans. Using the mean OD‐value + 1 standard deviation of 9 sera from patients solely infected with M. perstans (from the Gambia, where Loa loa is not endemic) as a cut‐off, 35 of the 44 microfilaraemic Loa loa patients and 2 of the 9 Gambian controls were positive. This shows that our method had a sensitivity of 80% and a specificity of 78%. Among the remaining 178 subjects who had no microfilariae of Loa loa, as many as 97 (55%) had significant levels of specific IgG4 antibodies against Loa loa, suggesting that they carried occult loiasis. The mean IgG4 level in these putatively occult loiasis patients was slightly but significantly lower than in microfilaraemic subjects (P < 0.03). In conclusion, despite the limited sensitivity and specificity of our method, IgG4‐ ELISA at present is a very useful tool in estimating the real prevalence of loiasis in epidemiological surveys and at the individual level can confirm the diagnosis of L. loa amicrofilaraemic subjects with clinical signs suggesting loiasis.

Cervicovaginal synthesis of IgG antibodies to the immunodominant 175-199 domain of the surface glycoprotein gp46 of human T-cell leukemia virus type I

Paired sera, saliva and cervicovaginal secretions from 17 HTLV‐I‐infected women (19–75 yr) were tested for total IgA and IgG, for IgA and IgG to the immunodominant region gp46/175‐Pro‐199, for serum IgG to the neutralizing domains gp46/190‐Pro‐199 and gp46/190‐Ser‐199, or for tax‐rex proviral HTLV‐DNA. Serum antibodies to gp46/175‐Pro‐199 were detected more frequently in the IgG (13/17) than in the IgA (5/17) isotypes. The majority (8/12) of anti‐gp46/175‐Pro‐199‐positive sera reacted also to gp46/190‐Pro‐199 or to gp46/190‐Ser‐199, demonstrating their neutralizing properties. In saliva, antibodies to gp46/175‐Pro‐199 were not generally detected. In cervicovaginal secretions, IgG to gp46/175‐Pro‐199, but not IgA, were detected in 6/15 (40%) patients. The mean specific activity of IgG to gp46/175‐Pro‐199 showed a trend to be higher in cervicovaginal secretions (218 ± 109) than in sera (14 ± 4). Furthermore, in all patients with cervicovaginal IgG to gp46/175‐Pro‐199, the cervicovaginal/serum ratio (19 ± 6) of anti‐gp46 IgG specific activities were markedly above 1. HTLV‐DNA was detected in 4/17 salivas, and in 3/15 cervicovaginal secretions, all from patients demonstrating cervico‐vaginal synthesis of IgG to gp46/175‐Pro‐199. In conclusion, IgG to gp46/175‐Pro‐199 in cervico‐vaginal secretions, when present, appear to be produced primarily locally because of local HTLV‐I excretion. Since anti‐gp46/175‐Pro‐199 antibodies usually support reactivities to neutralizing domains, their presence could be relevant for limiting HTLV‐I transmission via cervico‐vaginal secretions.

Hiv and Siv Envelope Glycoproteins Induce Phospholipase A2 Activation in Human and Macaque Lymphocytes

We investigated the early interactions between HIV-1, HIV-2, and simian immunodeficiency virus (SIV) envelope glycoproteins gp120(IIIB), gp105(ROD), and gp120(mac251), and human and macaque cells of the lymphocytic series. Our results demonstrate that the soluble viral glycoproteins induce a specific phospholipase A2 (PLA2) activation in lymphocytes through CD4. This PLA2 activation was induced after envelope glycoprotein-CD4 interaction and, because of its local membrane-destabilizing effect, may have important implications for preparing the lymphocyte membrane for fusion with the viral particle. However, this effect is not sufficient to accomplish fusion. These data indicate that the specific step of fusion may be downstream from PLA2 activation.