Differences in physiological response to increased seawater temperature in nearshore and offshore corals in northern Vietnam.

Effects of elevated seawater temperature show high spatial heterogeneity and variation within and among coral species. The objective of this study was to investigate how two coral species, Porites lutea and Galaxea fascicularis, from two high latitude reefs differently exposed to chronic disturbance, respond to elevated seawater temperatures. Corals were collected from reefs nearshore (i.e. subjected to high sediment load, higher chlorophyll α concentrations, turbidity etc.) and offshore (i.e. less exposed). The corals were exposed in the lab to gradually increasing temperatures (25.5-33.5 °C) for 72 h after which they were allowed to recover to ambient temperature (25.5 °C) for 24 h. Production and respiration were measured after 24, 48, 72 and 96 h. The results show that P. lutea from nearshore reefs suffered an initial decrease in gross primary production/respiration (GP/R) ratio after 24 h, after only a moderate temperature increase (+2 °C, from 25.5 to 27.5 °C), while there was no difference in GP/R ratio between heat-exposed and controls the other days, indicating that the chronic disturbance in the nearshore reef had no effect on their thermotolerance. Furthermore, P. lutea from the offshore reef showed a decrease in GP/R ratio both after 24 h and 72 h (33.5 °C) of exposure. In comparison, G. fascicularis showed a decrease in GP/R ratio after 48 h, 72 h and 96 h of exposure for the nearshore corals. Also, after 72 h these corals had withdrawn their polyps. There were no differences between heat-treated and controls for the offshore G. fascicularis. This implies that the chronically disturbed G. fascicularis had lower thermotolerance when exposed to a temperature increase. This study, hence, shows that the response of corals to elevated seawater temperature varies with species and environmental background history.

Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals.

We have previously associated high natural killer (NK)-cell activity and protection against HIV-1 infection in Vietnamese exposed uninfected intravascular drug users (EUs). Considering that activating and inhibitory signals sensed by NK-cell receptors regulate NK-cell activation, we performed phenotypic and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) transcript analyses of the NK-cell receptor (NKR) repertoire in 25 EUs, 19 HIV(+) intravenous drug users, and 26 uninfected blood donors. Although NK-cell activation was not linked to a unique NKR repertoire in EUs, various patterns consistent with NK-cell activation were detected in EUs: high KIR3DS1/KIR3DL1 ratio associated with down-regulated KIR3DL1 transcript levels, KIR2DL3(+) low-affinity receptor expansion associated to group HLA-C1 ligand in 2DS2(-)/2DL2(-) EUs, enhanced NKG2C/NKG2A ratio, and increased CD69 expression. Remarkably, EUs exhibited high constitutive degranulation activity in the absence of exogenous stimulation, as shown by the CD107a assay. Furthermore, CD161 expression was increased within the CD107a(+) NK-cell compartment. Our results suggest that in response to viral exposition, particular genetic or regulated features of the NKR repertoire of EUs contribute to their high constitutive NK-cell potential. This might allow NK cells to generate a more rapid and effective immune response to HIV-1, thereby contributing to prevention toward infection.

Systemic immune activation in HIV-1-exposed uninfected Vietnamese intravascular drug users.

To assess immunological parameters, including markers of immune activation, in highly HIV-1-exposed uninfected (EU) Vietnamese intravascular drug users (IDUs) in comparison with HIV-1-infected IDUs and HIVunexposed controls, we determined peripheral lymphocyte phenotypes in fresh whole blood samples from 32 EU IDUs, 28 HIV+ IDUs, and 26 blood donors. We found higher levels of activation markers (CD38, HLADR) on CD4+ and CD8+ T cells, lower percentages of naive CD4+ and CD8+ T cells, higher percentages of CD8+ T cells and of CD8+ T cells expressing CD25, and lower levels of CXCR4+CD4+ T cells in EU IDUs than in unexposed controls. Despite several differences in CD4+ and CD8+ T cell subset phenotypes, both EU and HIV+ IDUs exhibited a pattern of peripheral immune activation. Lymphocyte activation in EU IDUs may reflect immune stimulation driven by viral infections other than HIV-1 and/or allogeneic stimulation associated with needle sharing. Our results suggest that immune activation does not necessarily favor HIV-1 transmission, but, on the contrary, may alter the susceptibility of EUs to HIV-1 infection and contribute to their resistance.

New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia.

BACKGROUND: Despite multiple exposure to HIV-1, some individuals remain uninfected. This resistance has been associated with homozygosity for a 32 base pair deletion in the gene for the CCR5 receptor. This variant occurs frequently in Caucasians but is extremely rare in Asians or Africans. OBJECTIVE: To identify variations in CCR5 receptor gene that affect susceptibility to HIV infection in non-Caucasians. METHODS: CCR5 coding region polymorphisms were screened in three groups of Vietnamese subjects: 47 HIV-1 infected intravascular drug users, 50 highly HIV-1-exposed but seronegative intravascular drug users and 37 HIV-1-unexposed seronegative individuals. DNA was analysed by denaturing high performance liquid chromatography; this was followed by examination of the biochemical and HIV coreceptor properties of the coding regions. RESULTS: Five CCR5 coding region variants were identified in this Vietnamese population. The S185R, I254T and C269F mutations have not been previously described; G106R and R223Q have already been found in other Asian populations, but the functional properties of G106R is not known. These variants differed in biochemical and HIV coreceptor properties. S185R and I254T variants had receptor and coreceptor activities comparable to that of the wild type, whereas C269F and G106R behaved differently. This latter pair are poorly expressed at the cell surface, weakly bind macrophage inflammatory protein 1beta (CCL4) and RANTES (CCL5), and display reduced HIV-1 coreceptor efficiency. CONCLUSIONS: Among the five CCR5 variants found in this Vietnamese population, G106R and C269F displayed significant modifications of their receptor and coreceptor properties, which may contribute to susceptibility to HIV-1 infection and/or disease progression within this population.

Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected Vietnamese intravascular drug users.

We addressed the role of innate immunity in the protection against HIV-1 infection by studying NK cell function in 37 Vietnamese intravascular drug users (IDUs), who appeared to remain HIV-1 uninfected despite many years of high-risk exposure (exposed uninfected, EU), 10 IDUs who underwent seroconversion and 28 unexposed blood donors. Main results were: NK cell lytic activities against both the NK-susceptible K562 cell line and the NK-resistant Daudi cell line were significantly augmented in EU IDUs compared with either controls or seroconverters before or after seroconversion; NK cells producing the cytokines IFN-gamma and TNF-alpha and the beta chemokines CCL3, CCL4, and CCL5 were also increased in the EU IDUs, either after in vitro activation or without stimulation. The finding of an enhanced NK cell function in EU IDUs, especially compared with IDUs who became HIV-1 infected, supports the hypothesis that NK cells contribute to the protection against HIV-1 infection.

CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam.

OBJECTIVE: To identify mechanisms of resistance to HIV-1 infection in exposed uninfected individuals. DESIGN: We examined in-vitro cell susceptibility to HIV-1 infection in highly exposed Vietnamese intravascular drug users (IDU) who, despite a history of more than 10 years of drug use and a high prevalence of other blood-borne viral infections, remain apparently HIV uninfected. METHODS: Forty-five exposed uninfected IDU and 50 blood donors were included in the study. Peripheral blood mononuclear cells (PBMC) or CD4 cell susceptibilities to HIV infection were evaluated using three HIV-1 isolates with different tropisms. Polymerase chain reaction analysis of HIV-1-DNA replication intermediates was used to characterize the restriction of HIV-1 replication in CD4 cells. Homologous CD8 cells were mixed with infected CD4 cells to evaluate their role in virus suppression. RESULTS: We observed a relative resistance to PBMC infection with HIV-1 in 21 out of 45 exposed uninfected IDU, but only in five out of 50 unexposed controls (P < 0.001). PBMC resistance was related either to an inhibition of HIV-1 replication in CD4 cells or to CD8 cell-mediated viral suppression. HIV-1 replication in CD4 cells was restricted at the early stages of the viral cycle. CONCLUSION: Reduced PBMC susceptibility to HIV-1 infection was associated with resistance to infection in exposed uninfected IDU. Distinct mechanisms are involved in in-vitro resistance and may contribute to the apparent protection from HIV-1 transmission in this systemically exposed population.