Search

Recombinant influenza viruses hold promise as vectors for vaccines to prevent transmission of mucosal pathogens. In this study, we generated a recombinant WSN/TatΔ 51-59 virus in which Tat protein lacking residues 51 to 59 of the basic domain was inserted into the N-terminus of the hemagglutinin (HA) of A/WSN/33 virus. The TatΔ 51-59 insertion into the viral HA caused a 2-log reduction in viral titers in cell culture, compared with the parental A/WSN/33 virus, and severely affected virus replication in vivo. Nevertheless, Tat-specific antibodies and T cell responses were elicited upon a single intranasal immunization of BALB/c mice with WSN/TatΔ 51-59 virus. Moreover, Tat-specific immune responses were also detected following vaccine administration via the vaginal route. These data provide further evidence that moderately large HIV antigens can be delivered by chimeric HA constructs and elicit specific immune responses, thus increasing the options for the potential use of recombinant influenza viruses, and their derivatives, for prophylactic and therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Mauritian cynomolgus macaques (MCM) are widely used in human immunodeficiency virus research because of their restricted major histocompatibility complex (MHC) diversity which provides the opportunity to address the influence of host factors on vaccine studies. We herein report the impact of MHC haplotype on the outcome of 21 MCM infections with the CCR5-tropic simian/human immunodeficiency virus (SHIV)SF162P4cy. MCM were susceptible to SHIVSF162P4cy infection as shown by viremia and loss of CD4+ T cells. A significant association between haplotype M7 (class I A, I B, II) and persistent viremia was observed in chronic phase, whereas recombinant class I A haplotype was associated with a reduction of viral RNA during acute infection. Class I B M4 haplotype displayed significantly lower acute phase provirus copy numbers. In addition, statistical analysis indicated a detrimental effect of haplotype M4 (class I A, I B) on the course of infection as indicated by lower CD4+ T-cell levels during chronic infection. A decrease in post-acute phase CD4+ T-cell numbers was also observed in haplotype M2 animals. This is the first report that documents the effects of host MHC class I and II molecules on the SHIVSF162P4cyinfection in MCM, particularly with regard to the association between recombinant class I A, M4, and M7 haplotypes and the dynamic of viral replication and level of CD4+ T cells. [ABSTRACT FROM AUTHOR]

Simian–human immunodeficiency virus (SHIV) 89.6P is considered to be one of the most pathogenic chimeric viruses in rhesus macaques. However, when crossing from one to another species of monkeys the pathogenicity of this virus may be affected. By using SHIV-89.6Pcy243, a virus obtained by passaging SHIV-89.6P in cynomolgus macaques, we investigated the dynamics of viral replication and the impact of the inoculum size (from 10 up to 50 monkey infectious dose) on the progression of the infection in 22 cynomolgus macaques. SHIV-89.6Pcy243 caused massive depletion of CD4+ T-cells within 4 weeks of the inoculum, followed by an irreversible immune deficiency in a high proportion of the infected monkeys. This study demonstrates that SHIV-89.6Pcy243 is pathogenic in cynomolgus macaques and that the dynamics of the viral replication and the rate of clinical progression depend on the size of the inoculum. Our findings provide unique and relevant data, particularly with regard to the value of the in vivo titration used to select the most appropriate infectious dose to study the “virus-host” interplay. [ABSTRACT FROM AUTHOR]

Cynomolgus macaques are frequently used in biomedical research. However, in contrast to their closest relative, the rhesus macaque, little is known about their Mhc genes except for the DQB1 locus. In this study, 33 DRB-sequences belonging to 17 allelic lineages were detected in a total of 68 macaques, 58 originating from Mauritius and 10 from China. The majority of the sequences were detected in the few macaques from China, confirming the low degree of genetic variation in macaques from Mauritius. In summary, the DRB region in cynomolgus macaques is polymorphic. The sequences belong in general to the same allelic lineages as in their closest relative, the rhesus macaque. Two exon 2 DNA sequences were identical in both species and may represent a trans-species origin. In addition, protein sequences of members of the DRB*W1 lineage seem to be rather conserved in the three macaque species examined so far. Six DRB-haplotypes were detected in the macaques from Mauritius. While single DRB-alleles or some protein sequences seemed to be conserved among macaque species, we could not detect any evidence for a trans-species conservation of a complete DRB region. Overall, the data indicate that reorganization of the DRB region by recombination is a major force in creating diversity in cynomolgus macaques as it is in rhesus macaques. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper we addressed the expression of the HIV co-receptors CXCR-4 and CCR-5 in human thymocytes by phenotypic, molecular and functional approaches. Cytofluorimetric analysis disclosed that CXCR-4 was constitutively expressed by freshly isolated thymocytes (~10 000 molecules/cell in about 30% of thymocytes); the receptor was endowed with functional activity, as it mediated polarization, migration and intracellular Ca2+ increase in response to its ligand, SDF-1. On the contrary, CCR-5 expression in freshly isolated thymocytes was significantly lower (<4000 molecules/cell in less than 5% of the cells), and no functional response to CCR-5 agonists could be documented. Northern blot analysis of freshly isolated thymocytes showed high CXCR-4 mRNA levels, whereas the message for CCR-5 was barely detectable. On the other hand, a modest increase in the expression of CCR-5 was associated with in vitro thymocyte stimulation, and CCR-5 density at the cell surface attained CXCR-4 figures in most cases. None the less, no functional response to CCR-5 agonists could be documented in in vitro stimulated thymocytes. In vitro infection of thymocytes by CAT-expressing recombinant HIV bearing the envelope glycoproteins from different isolates showed that T-tropic strains, which use CXCR-4 as a co-receptor, were more efficient in infecting thymocytes than M-tropic strains, which preferentially use CCR-5. Altogether, these data indicate that expression of the major co-receptors involved in infection by M-tropic HIV strains is very poor in human thymocytes, and would suggest that thymocyte infection by M-tropic HIV strains may be a rare event in vivo . [ABSTRACT FROM AUTHOR]

Investigates the potential therapeutic utility of thalidomide (Thd), an effective inhibitor of tumor necrosis factor (TNF)-alpha in vitro, in cynomolgus monkeys at ten months after infection with simian immunodeficiency virus (SIV). Restoration by Thd of the proliferative responses to SIV peptides in monkeys infected with SIV; Non-observation of a reduction in either cell-associated viral load or plasma viral RNA among the SIV-infected monkeys during the two treatment cycles, when compared with the placebo group.

The influence of in vivo infection with the polycythemic substrain of Friend leukemia virus on noninducible ('natural') resistance against allogeneic normal or malignant grafts was studied in lethally irradiated mice. Parallel studies were performed on the NK system in the same experimental conditions. The results indicate that FLV-P infection of mice with full (DBA/2) vs partial (BALB/c and CD2F1) susceptibility did not suppress their in vivo natural resistance against bone marrow or El-4 leukemia cells. On the other hand, a decline in NK activity paralleled the progression of leukemic disease in the more susceptible DBA/2 hosts. [ABSTRACT FROM AUTHOR]

To assess the prevalence of HIV-1 infection and study selected risk factors among patients attending a clinic for sexually transmitted diseases in Rome, 1442 outpatients seen consecutively between 20 February and 12 December 1989 were anonymously tested for anti-HIV-1. An evaluation of the trend of the HIV-1 infection was attempted by comparing the results of the present study with those obtained from a similar sample studied in 1986 in the same clinic. The overall estimated prevalence of anti-HIV-1 was 1.2 % among heterosexual non-drug user subjects and 16.1 % among homosexual or bisexual men. The anti-HIV-1 seropositivity was significantly higher in heterosexual subjects who reported sexual contact with intravenous drug users, as compared with those who did not report such exposure (12.5 % vs 0.8 %, p<0.005). Comparing the present data with those of a study conducted in 1986 in the same clinic, a lower prevalence of anti-HIV-1 was found among heterosexual subjects (1.2 % in 1989 vs 6.0 % in 1986, p<0.001). The availability after 1986 of several outpatient facilities attracting seropositive subjects and a change in the sexual behaviour of anti-HIV-1 positive subjects could explain this finding. Twenty percent of the heterosexual subjects and 62 % of the homosexual or bisexual men reported consistent use of condoms. In both heterosexual subjects and homosexual/bisexual men only the number of sexual partners in the previous year seemed to be related to the use of condoms, a higher proportion of subjects with two or more partners reporting the use of condoms, as compared with monogamous subjects (29.5 % vs 11.5 %, p<0.001 and 68.0 % vs 37.0 %, p<0.005). The infrequent use of condoms, in particular among heterosexual subjects, suggests that education campaigns conducted so far were partly effective. [ABSTRACT FROM AUTHOR]