There is an increasing proportion of HIV-positive patients exposed to all licensed classes of ant... more There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2–5.2], CD4 lymphocyte count 150/mm3 (IQR 60–274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load <500 copies/ml. Conversely, the CD4 count halved from the bas...
Dead Sea climatotherapy (DSC) is a well‐established therapeutic modality for the treatment of sev... more Dead Sea climatotherapy (DSC) is a well‐established therapeutic modality for the treatment of several diseases, including atopic dermatitis. Skin microbiome studies have shown that skin microbiome diversity is anticorrelated with both atopic dermatitis severity and concurrent Staphylococcus aureus overgrowth. This study aimed to determine whether DSC induces skin microbiome changes concurrent with clinical improvements in atopic dermatitis. We sampled 35 atopic dermatitis patients and ten healthy controls on both the antecubital and popliteal fossa. High‐resolution microbial community profiling was attained by sequencing multiple regions of the 16S rRNA gene. Dysbiosis was observed in both lesional and nonlesional sites, which was partially attenuated following treatment. Severe AD skin underwent the most significant community shifts, and Staphylococcus epidermidis, Streptococcus mitis and Micrococcus luteus relative abundance were significantly affected by Dead Sea climatotherapy. ...
HIV infection and disease are determined to a large extent by the host's immune response. Exp... more HIV infection and disease are determined to a large extent by the host's immune response. Exposure to the virus alone does not lead necessarily to long-lasting infection and the progress of HIV infection once established varies in different individuals. The development of host immunity, while either "protective" or "enhancing," will determine all these outcomes.
An elderly woman who had a typical polymyalgia rheumatica (PMR) syndrome, associated with severe ... more An elderly woman who had a typical polymyalgia rheumatica (PMR) syndrome, associated with severe headache, was considered to have giant cell arteritis despite negative temporal artery biopsies and was treated with corticosteroids. At autopsy, no arteritis, but a large temporal lobe meningioma, was found as the cause of her headache. Both PMR and meningiomas are frequent in elderly patients, and overlapping symptoms may occur. Patients with PMR and headache should be fully investigated to exclude an occult meningioma or other disease, especially when no positive histologic evidence of temporal arteritis can be obtained.
The replication cycle of any virus involves a number of steps, beginning with specific attachment... more The replication cycle of any virus involves a number of steps, beginning with specific attachment to a cell surface receptor leading eventually to production of progeny viruses by infected cells. In the case of the immunodeficiency virus type-1 (HIV-1), the first step involves a specific interaction between the gp120 viral envelope surface protein and specific CD4 receptor sites at the cell surface. This is followed by penetration of the virus into cells and the formation of proviral double-stranded DNA from single-stranded viral RNA, a process mediated through the action of the viral enzyme called reverse transcriptase. This, in turn, leads to the migration of proviral DNA into the nucleus of the cell and the integration of such DNA within the host cell genome. Finally both viral RNA and viral proteins are produced by the cell's genetic apparatus and new viruses are assembled at the cell surface. The fact that integration of viral DNA into host cell chromosomes occurs means tha...
p53 is a potent tumor suppressor, whose biological effects are largely due to its function as a t... more p53 is a potent tumor suppressor, whose biological effects are largely due to its function as a transcriptional regulator. Here we report that, in addition to regulating the expression of hundreds of protein-coding genes, p53 also modulates the levels of microRNAs (miRNAs). Specifically, p53 can induce expression of microRNA-34a (miR-34a) in cultured cells as well as in irradiated mice, by binding to a perfect p53 binding site located within the gene that gives rise to miR-34a. Processing of the primary transcript into mature miR-34a involves the excision of a 30 kb intron. Notably, inactivation of miR-34a strongly attenuates p53-mediated apoptosis in cells exposed to genotoxic stress, whereas overexpression of miR-34a mildly increases apoptosis. Hence, miR-34a is a direct proapoptotic transcriptional target of p53 that can mediate some of p53's biological effects. Perturbation of miR-34a expression, as occurs in some human cancers, may thus contribute to tumorigenesis by attenuating p53-dependent apoptosis.
Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in c... more Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in clinical practice. Ultradeep pyrosequencing has shown to be effective in detecting such mutations. The lack of a standardized commercially based assay limits the wide use of this method in clinical settings. 454 Life Sciences (Roche) is developing an HIV ultradeep pyrosequencing assay for their benchtop sequencer. We assessed the prototype plate in the clinical laboratory. Plasma samples genotyped by the standardized TruGene kit were retrospectively tested by this assay. Drug-treated subjects failing therapy and drug-naive patients were included. DRM analysis was based on the International AIDS Society USA DRM list and the Stanford algorithm. The prototype assay detected all of the DRMs detected by TruGene and additional 50 low-abundance DRMs. Several patients had low-abundance D67N, K70R, and M184V reverse transcriptase inhibitor mutations that persisted long after discontinuation of the...
We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of an... more We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of antibodies to HTLVI and HTLVIII and their correlation with impairments of the immune system and serum interferon (IFN). Seropositivity for HTLVI, HTLVIII, or both was found in 1.4, 8.3, and 0%, respectively. Significant decreases in the total peripheral T cells, TH cells, and TH/Ts ratio as well as elevated cdFN serum levels were found in the MHS group in comparison with normal controls. Although no difference in the prevalence of either immune derangements or elevated serum IFN was observed between HTLVIII/LAV-seropositive and HTLVIII/ LAV-seronegative MHS, the decreases in total T cells, Tn cells, and T~/Ts ratios were significantly greater in the seropositive MHS. These results indicate that (a) immune impairments and IFN system activation occur commonly in homosexuals, precede their exposure to HTLVIII/ LAV, and probably reflect this group's increased risk for AIDS and (b) HTLVIII/LAV infection of MHS aggravates further their preexisting immune impairments.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012
Background and MethodsSmall and microRNAs (Mirs) are small noncoding RNAs that regulate gene expr... more Background and MethodsSmall and microRNAs (Mirs) are small noncoding RNAs that regulate gene expression by posttranscriptional suppression. They play a major role in controlling host response and viral replication in several viral infections, but their role during HIV infection has been a controversial issue. We have applied our integrated bioinformatics-biological platform including deep sequencing for small RNA profiling and detection for the study of host and viral encoded small RNAs during HIV infection. ResultsComparing infected and non-infected cells from both cell lines and freshly infected PBMC and CD4 T cells, we report here on the differential expression of several predicted, validated viral encoded Mirs and differentially expressed host Mirs. Deep sequencing revealed a very high number of reads for small nonMir RNA located in specific loci of the HIV genome, the presence of which have also been confirmed by RT-PCR. Suppression of some of these host Mirs and the highly abundant small RNAs, led to suppressed viral replication and therefore seems to contribute to the latency phase of HIV infection. The bioinformatically predicted target of these small RNAs and their biologic validation suggests that they target genes regulating immune activation and Interferon alpha. Conclusions1) HIV infection is associated with differential expression of several Mirs and small noncoding RNAs. 2) Some of the viral encoded Mirs and small RNAs have a direct effect on viral replication and latency. 3) Genes controlling immune activation and the Interferon system are under direct control of some of these RNA molecules. 4) Small noncoding RNAs may have a key role in latency and persistence of HIV infection in HIV reservoirs.
In view of the natural resistance to infection by HIV and occasional delayed clinical manifestati... more In view of the natural resistance to infection by HIV and occasional delayed clinical manifestation of the disease, as also the fact that the virus is able to enter only cells that express CD4 and a co-receptor, we initiated a search for a soluble co-receptor that might compete with its membrane counterpart. Using a sandwich ELISA system, a soluble human CCR5 receptor (sCCR5) was indeed detected in the circulation. Immunoprecipitation of sCCR5-positive plasma samples from Israelis of Ethiopian and non-Ethiopian origin with mAb 2D7, a conformation-dependent anti-CCR5 antibody, revealed the presence of an approximately 22 kDa protein. A panel of antibodies directed against the membrane receptor was used to characterize the structure of the soluble CCR5: mAb CTC8, recognizing the N-terminal sequence of the protein, 10YDIN13; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;multidomain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; mAbs FAB181B and FAB183B that are dependent upon the presence of Q93 and D95 in ECL1 and K171 and E172 in ECL2A, and mAb FAB182B, recognizing the stretch 184YSQYQF189, which spans the C-terminal part of the second extracellular loop. The presence of short soluble CCR5 in human plasma has not been previously described. Among HIV-negative non-Ethiopian Israelis, 20.4% were sCCR5-positive, as against only 10.5% in HIV-positives. However, 7.1% of HIV-negative Ethiopian Israelis were sCCR5 positive, as were 5.6% HIV-positives. Plasma concentrations of MIP-1beta, the CCR5 agonist, were twice as high in sCCR5-positives (140.8+/-25.8 pg/ml) as in the sCCR5-negatives (77.6+/-11.0 pg/ml, P=0.0157). A significant positive correlation between plasma levels of sCCR5 and MIP-1beta was found (Fig. 4, r=0.8, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001).
Australian Journal of Experimental Biology and Medical Science, 1969
INABILITY OF PERIPHERAL LYMPHOID CELLS OF AGAMMAGLOBULINAEMIC PATIENTS TO BIND RADIOIODINATED ALB... more INABILITY OF PERIPHERAL LYMPHOID CELLS OF AGAMMAGLOBULINAEMIC PATIENTS TO BIND RADIOIODINATED ALBUMINS
HIV coreceptors play a major role in determining susceptibility and HIV cell tropism. The present... more HIV coreceptors play a major role in determining susceptibility and HIV cell tropism. The present work studied whether the high expression of these coreceptors found on lymphocytes and monocytes of Ethiopian immigrants to Israel (ETH) is the result of environmental and/or constitutive genetic factors. The study of 26 ETH shortly after their arrival to Israel (new ETH), 22 ETH in Israel over 7 years (old ETH), and 20 Caucasian Israelis (non-ETH) enabled us to address this issue. The new ETH had elevated levels of activated HLA-DR+CD4+ and CD38+CD8+ cells in comparison with both old ETH and non-ETH groups (P &lt; 0.01), most probably related to chronic helminthic infections. Surface CCR5 expression, i.e., the percentage of CCR5+ cells and the number of CCR5 molecules/cell, was higher (2- to 3- and 8- to 31-fold, respectively) in activated than in nonactivated CD4+ cells, in all groups. However, CCR5 expression, in both activated and nonactivated CD4+ cells, was higher in both ETH groups than in the non-ETH group. CXCR4 expression was higher in nonactivated CD4+ cells in all groups and was also higher in both ETH groups, in both activated and nonactivated CD4+ cells, than in the non-ETH group. These findings suggest that constitutive factors, in addition to immune activation caused by environmental factors, account for the elevated expression of CCR5 and CXCR4 on CD4+ cells of ETH. This increased HIV coreceptor expression may make ETH more susceptible to HIV infection and may account in part for the rapid spread of AIDS in Ethiopia and the rest of Africa as well.
SUMMARYViral cofactors may be important in the pathogenesis of HIV infection and the development ... more SUMMARYViral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV– and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed a...
There is an increasing proportion of HIV-positive patients exposed to all licensed classes of ant... more There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2–5.2], CD4 lymphocyte count 150/mm3 (IQR 60–274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load <500 copies/ml. Conversely, the CD4 count halved from the bas...
Dead Sea climatotherapy (DSC) is a well‐established therapeutic modality for the treatment of sev... more Dead Sea climatotherapy (DSC) is a well‐established therapeutic modality for the treatment of several diseases, including atopic dermatitis. Skin microbiome studies have shown that skin microbiome diversity is anticorrelated with both atopic dermatitis severity and concurrent Staphylococcus aureus overgrowth. This study aimed to determine whether DSC induces skin microbiome changes concurrent with clinical improvements in atopic dermatitis. We sampled 35 atopic dermatitis patients and ten healthy controls on both the antecubital and popliteal fossa. High‐resolution microbial community profiling was attained by sequencing multiple regions of the 16S rRNA gene. Dysbiosis was observed in both lesional and nonlesional sites, which was partially attenuated following treatment. Severe AD skin underwent the most significant community shifts, and Staphylococcus epidermidis, Streptococcus mitis and Micrococcus luteus relative abundance were significantly affected by Dead Sea climatotherapy. ...
HIV infection and disease are determined to a large extent by the host's immune response. Exp... more HIV infection and disease are determined to a large extent by the host's immune response. Exposure to the virus alone does not lead necessarily to long-lasting infection and the progress of HIV infection once established varies in different individuals. The development of host immunity, while either "protective" or "enhancing," will determine all these outcomes.
An elderly woman who had a typical polymyalgia rheumatica (PMR) syndrome, associated with severe ... more An elderly woman who had a typical polymyalgia rheumatica (PMR) syndrome, associated with severe headache, was considered to have giant cell arteritis despite negative temporal artery biopsies and was treated with corticosteroids. At autopsy, no arteritis, but a large temporal lobe meningioma, was found as the cause of her headache. Both PMR and meningiomas are frequent in elderly patients, and overlapping symptoms may occur. Patients with PMR and headache should be fully investigated to exclude an occult meningioma or other disease, especially when no positive histologic evidence of temporal arteritis can be obtained.
The replication cycle of any virus involves a number of steps, beginning with specific attachment... more The replication cycle of any virus involves a number of steps, beginning with specific attachment to a cell surface receptor leading eventually to production of progeny viruses by infected cells. In the case of the immunodeficiency virus type-1 (HIV-1), the first step involves a specific interaction between the gp120 viral envelope surface protein and specific CD4 receptor sites at the cell surface. This is followed by penetration of the virus into cells and the formation of proviral double-stranded DNA from single-stranded viral RNA, a process mediated through the action of the viral enzyme called reverse transcriptase. This, in turn, leads to the migration of proviral DNA into the nucleus of the cell and the integration of such DNA within the host cell genome. Finally both viral RNA and viral proteins are produced by the cell's genetic apparatus and new viruses are assembled at the cell surface. The fact that integration of viral DNA into host cell chromosomes occurs means tha...
p53 is a potent tumor suppressor, whose biological effects are largely due to its function as a t... more p53 is a potent tumor suppressor, whose biological effects are largely due to its function as a transcriptional regulator. Here we report that, in addition to regulating the expression of hundreds of protein-coding genes, p53 also modulates the levels of microRNAs (miRNAs). Specifically, p53 can induce expression of microRNA-34a (miR-34a) in cultured cells as well as in irradiated mice, by binding to a perfect p53 binding site located within the gene that gives rise to miR-34a. Processing of the primary transcript into mature miR-34a involves the excision of a 30 kb intron. Notably, inactivation of miR-34a strongly attenuates p53-mediated apoptosis in cells exposed to genotoxic stress, whereas overexpression of miR-34a mildly increases apoptosis. Hence, miR-34a is a direct proapoptotic transcriptional target of p53 that can mediate some of p53's biological effects. Perturbation of miR-34a expression, as occurs in some human cancers, may thus contribute to tumorigenesis by attenuating p53-dependent apoptosis.
Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in c... more Detection of low-abundance drug resistance mutations (DRMs) of HIV-1 is an evolving approach in clinical practice. Ultradeep pyrosequencing has shown to be effective in detecting such mutations. The lack of a standardized commercially based assay limits the wide use of this method in clinical settings. 454 Life Sciences (Roche) is developing an HIV ultradeep pyrosequencing assay for their benchtop sequencer. We assessed the prototype plate in the clinical laboratory. Plasma samples genotyped by the standardized TruGene kit were retrospectively tested by this assay. Drug-treated subjects failing therapy and drug-naive patients were included. DRM analysis was based on the International AIDS Society USA DRM list and the Stanford algorithm. The prototype assay detected all of the DRMs detected by TruGene and additional 50 low-abundance DRMs. Several patients had low-abundance D67N, K70R, and M184V reverse transcriptase inhibitor mutations that persisted long after discontinuation of the...
We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of an... more We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of antibodies to HTLVI and HTLVIII and their correlation with impairments of the immune system and serum interferon (IFN). Seropositivity for HTLVI, HTLVIII, or both was found in 1.4, 8.3, and 0%, respectively. Significant decreases in the total peripheral T cells, TH cells, and TH/Ts ratio as well as elevated cdFN serum levels were found in the MHS group in comparison with normal controls. Although no difference in the prevalence of either immune derangements or elevated serum IFN was observed between HTLVIII/LAV-seropositive and HTLVIII/ LAV-seronegative MHS, the decreases in total T cells, Tn cells, and T~/Ts ratios were significantly greater in the seropositive MHS. These results indicate that (a) immune impairments and IFN system activation occur commonly in homosexuals, precede their exposure to HTLVIII/ LAV, and probably reflect this group's increased risk for AIDS and (b) HTLVIII/LAV infection of MHS aggravates further their preexisting immune impairments.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012
Background and MethodsSmall and microRNAs (Mirs) are small noncoding RNAs that regulate gene expr... more Background and MethodsSmall and microRNAs (Mirs) are small noncoding RNAs that regulate gene expression by posttranscriptional suppression. They play a major role in controlling host response and viral replication in several viral infections, but their role during HIV infection has been a controversial issue. We have applied our integrated bioinformatics-biological platform including deep sequencing for small RNA profiling and detection for the study of host and viral encoded small RNAs during HIV infection. ResultsComparing infected and non-infected cells from both cell lines and freshly infected PBMC and CD4 T cells, we report here on the differential expression of several predicted, validated viral encoded Mirs and differentially expressed host Mirs. Deep sequencing revealed a very high number of reads for small nonMir RNA located in specific loci of the HIV genome, the presence of which have also been confirmed by RT-PCR. Suppression of some of these host Mirs and the highly abundant small RNAs, led to suppressed viral replication and therefore seems to contribute to the latency phase of HIV infection. The bioinformatically predicted target of these small RNAs and their biologic validation suggests that they target genes regulating immune activation and Interferon alpha. Conclusions1) HIV infection is associated with differential expression of several Mirs and small noncoding RNAs. 2) Some of the viral encoded Mirs and small RNAs have a direct effect on viral replication and latency. 3) Genes controlling immune activation and the Interferon system are under direct control of some of these RNA molecules. 4) Small noncoding RNAs may have a key role in latency and persistence of HIV infection in HIV reservoirs.
In view of the natural resistance to infection by HIV and occasional delayed clinical manifestati... more In view of the natural resistance to infection by HIV and occasional delayed clinical manifestation of the disease, as also the fact that the virus is able to enter only cells that express CD4 and a co-receptor, we initiated a search for a soluble co-receptor that might compete with its membrane counterpart. Using a sandwich ELISA system, a soluble human CCR5 receptor (sCCR5) was indeed detected in the circulation. Immunoprecipitation of sCCR5-positive plasma samples from Israelis of Ethiopian and non-Ethiopian origin with mAb 2D7, a conformation-dependent anti-CCR5 antibody, revealed the presence of an approximately 22 kDa protein. A panel of antibodies directed against the membrane receptor was used to characterize the structure of the soluble CCR5: mAb CTC8, recognizing the N-terminal sequence of the protein, 10YDIN13; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;multidomain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; mAbs FAB181B and FAB183B that are dependent upon the presence of Q93 and D95 in ECL1 and K171 and E172 in ECL2A, and mAb FAB182B, recognizing the stretch 184YSQYQF189, which spans the C-terminal part of the second extracellular loop. The presence of short soluble CCR5 in human plasma has not been previously described. Among HIV-negative non-Ethiopian Israelis, 20.4% were sCCR5-positive, as against only 10.5% in HIV-positives. However, 7.1% of HIV-negative Ethiopian Israelis were sCCR5 positive, as were 5.6% HIV-positives. Plasma concentrations of MIP-1beta, the CCR5 agonist, were twice as high in sCCR5-positives (140.8+/-25.8 pg/ml) as in the sCCR5-negatives (77.6+/-11.0 pg/ml, P=0.0157). A significant positive correlation between plasma levels of sCCR5 and MIP-1beta was found (Fig. 4, r=0.8, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001).
Australian Journal of Experimental Biology and Medical Science, 1969
INABILITY OF PERIPHERAL LYMPHOID CELLS OF AGAMMAGLOBULINAEMIC PATIENTS TO BIND RADIOIODINATED ALB... more INABILITY OF PERIPHERAL LYMPHOID CELLS OF AGAMMAGLOBULINAEMIC PATIENTS TO BIND RADIOIODINATED ALBUMINS
HIV coreceptors play a major role in determining susceptibility and HIV cell tropism. The present... more HIV coreceptors play a major role in determining susceptibility and HIV cell tropism. The present work studied whether the high expression of these coreceptors found on lymphocytes and monocytes of Ethiopian immigrants to Israel (ETH) is the result of environmental and/or constitutive genetic factors. The study of 26 ETH shortly after their arrival to Israel (new ETH), 22 ETH in Israel over 7 years (old ETH), and 20 Caucasian Israelis (non-ETH) enabled us to address this issue. The new ETH had elevated levels of activated HLA-DR+CD4+ and CD38+CD8+ cells in comparison with both old ETH and non-ETH groups (P &lt; 0.01), most probably related to chronic helminthic infections. Surface CCR5 expression, i.e., the percentage of CCR5+ cells and the number of CCR5 molecules/cell, was higher (2- to 3- and 8- to 31-fold, respectively) in activated than in nonactivated CD4+ cells, in all groups. However, CCR5 expression, in both activated and nonactivated CD4+ cells, was higher in both ETH groups than in the non-ETH group. CXCR4 expression was higher in nonactivated CD4+ cells in all groups and was also higher in both ETH groups, in both activated and nonactivated CD4+ cells, than in the non-ETH group. These findings suggest that constitutive factors, in addition to immune activation caused by environmental factors, account for the elevated expression of CCR5 and CXCR4 on CD4+ cells of ETH. This increased HIV coreceptor expression may make ETH more susceptible to HIV infection and may account in part for the rapid spread of AIDS in Ethiopia and the rest of Africa as well.
SUMMARYViral cofactors may be important in the pathogenesis of HIV infection and the development ... more SUMMARYViral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV– and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed a...
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Papers by Zvi Bentwich