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It was a great honor for us to have served as co-chairs of the recent 16th International Conference on AIDS (Toronto, Canada, August 13–18, 2006). We were gratified that attendance eclipsed that of all previously held International AIDS conferences. Despite a few glitches, such as problems with registration at the start of the conference, most observers concurred that it went extremely well. In fact, the conference seems to have been judged a great success from both the scientific and social standpoints. (Published: 19 April 2007) doi:10.1186/1758-2652-9-2-15 Full text: BioMed Central: http://www.biomedcentral.com/1758-2652/content/9/2/15 PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758903/

This Commentary reflects on the success of the XVI International Conference on AIDS, that was held in Toronto between August 13–18, 2006. Not only was the Conference judged to have been a scientific success, it will probably also be recognized over time as having had important political impact. It is vital that scientists and policy-makers continue to be able to interact at these meetings as part of global efforts to combat the HIV epidemic.

In many cities, infectious disease and overdose epidemics are occurring among illicit injection drug users (IDUs). To reduce these concerns, Vancouver opened a supervised safer injecting facility in September 2003. Within the facility, people inject pre-obtained illicit drugs under the supervision of medical staff. The program was granted a legal exemption by the Canadian government on the condition that a 3-year scientific evaluation of its impacts be conducted. In this review, we summarize the findings from evaluations in those 3 years, including characteristics of IDUs at the facility, public injection drug use and publicly discarded syringes, HIV risk behaviour, use of addiction treatment services and other community resources, and drug-related crime rates. Vancouver's safer injecting facility has been associated with an array of community and public health benefits without evidence of adverse impacts. These findings should be useful to other cities considering supervised injecting facilities and to governments considering regulating their use.

In 2004, almost 5 million people became newly infected with HIV, emphasizing the continuous need for effective prevention strategies. The development of an effective preventive vaccine faces many difficulties and is not likely to occur within the next decade. Behavioural changes, such as consistent and correct condom use and abstinence from high-risk behaviour, probably contributed to the fall in HIV incidence recently reported in several African countries and in India [1]. Recently, it was shown that male circumcision reduced the risk of acquiring HIV by 60% [2] and the risk of male-to-female transmission by 30% [3]. However, behavioural interventions may not be able to curb the HIV epidemic as much as needed, prompting the need to find additional, more effective preventive strategies. There is also a need for “female-initiated intervention”. Women around the globe continue to be infected with HIV by their male partners and often feel unable to insist on condom use. Alternatives to behavioural strategies include those that are based on drugs. Anti-HIV vaginal microbicides, which may offer women a means of protecting themselves from infection, are currently being evaluated [4]. Also, rectally applied microbicides have proven to effectively prevent infection in macaques challenged via this transmission route [5]. However, like male circumcision, this strategy may not provide protection against other routes of HIV transmission, such as oral or intravenous transmission. Oral antiretroviral pre-exposure prophylaxis (PREP) in high-risk populations may be a more reliable tool in preventing transmission of HIV [6]. Limited animal model data suggest that antiretroviral drugs may prevent infection when taken prior to, at the time of, and/or after HIV exposure [7–10]. Theoretically, preventing HIV infection could be done by blocking any step in the HIV life cycle. Blocking a step prior to integration of proviral DNA into the host DNA is believed to have greater potential since this way the permanent integration of proviral HIV is averted.

The nucleotide transition G--A is known as a hypermutation due to its high prevalence in HIV-1 and other pathogens. However, the contribution of the G--A transition in the generation of drug resistance mutations is unknown . Our objective was to ascertain the rate of nucleotide substitutions in protease (PR) and reverse transcriptase (RT) in both untreated and treated HIV-1 patients. Genotypic analysis was performed on viruses from both treated and untreated patients with subtype B infections. Nucleotide genomic diversity was compared with a consensus subtype B reference virus. Then, the prevalence of resistance-associated mutations in different subgroups of treated patients was evaluated in relation to the patterns of nucleotide transitions. In untreated patients (n = 50) G--A was most prevalent, followed by A--G, C--T, and T--C transitions. In treated patients (n = 51), the prevalence of A--G was similar to that of G--A. Among mutations that confer resistance to antiretroviral drugs, M184V was present in 76% of treated patients and K70R in 31% (A--G transitions). Other frequent mutations in RT included T215Y (C--A and A--T substitutions), which was prevalent in 31% of treated patients. In PR, a L90M (T--A substitution) was prevalent in 47% of protease inhibitor (PI)-treated patients. In conclusion, the G--A transition was most prevalent in RT and PR among untreated patients. In contrast, A--G was the most prevalent transition in patients treated with antiretroviral drugs.

During virus assembly, all retroviruses specifically encapsidate two copies of full-length viral genomic RNA in the form of a non-covalently linked RNA dimer. The absolute conservation of this unique genome structure within the Retroviridae family is strong evidence that a dimerized genome is of critical importance to the viral life cycle. An obvious hypothesis is that retroviruses have evolved to preferentially package two copies of genomic RNA, and that dimerization ensures the proper packaging specificity for such a genome. However, this implies that dimerization must be a prerequisite for genome encapsidation, a notion that has been debated for many years. In this article, we review retroviral RNA dimerization and packaging, highlighting the research that has attempted to dissect the intricate relationship between these two processes in the context of HIV-1, and discuss the therapeutic potential of these putative antiretroviral targets.

Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy.

to –1·38 log10) (table). In one of five patients who received 250 mg and two of five patients on 750 mg, viral load went below detection. In the high-dose cohorts, the mean viral load stayed below the value at entry after a 7-day washout period (–0·22 to –0·27 log10), in contrast with placebo treated patients, who had +0·25 and +0·58 log10 increase in viral load. In order to evaluate the generation of resistant viruses under short-term monotherapy, half maximum inhibition values by the drug in cell culture (IC50) were determined from viruses isolated from the patients before and after therapy. IC50 values at entry were between 0·1 and 3 nmoL, except for patient 6 in the 750 mg group, who had a resistant virus at entry with an IC50 of 160 nmoL, containing a NNRTI resistance mutation as well as a zidovudineresistance mutation in virions derived from plasma and in cultured virus. Development of a less sensitive virus after treatment was seen in only one patient in the 750 mg study and one patient in the 1000 mg study. No correlation was seen between initial viral load and the probability for development of a less sensitive virus (data not shown). The elevations in IC50 values were moderate (15 and 2·2 nmoL, respectively) and correlated with a partial or full mutation at position 103 of the reverse transcriptase. In studies with nevirapine, resistant virus replaced wild type within 2–4 weeks in all patients. These data suggest that HBY097 and related compounds are promising second-generation NNRTIs, which could be included in first-line combination therapies.

The technique of peripheral lymphocyte stimulation in response to antigen was used to demonstrate the existence of cell-mediated anti-tumor immunity in chickens bearing tumors induced by avian sarcoma viruses. The expression of this anti-tumor response against virus-containing transformed cell culture supernatant fluids and cell extracts varied among animals in terms of time after inoculation with the oncogenic agent. Animals whose tumors had completely regressed rapidly lost the ability to mount such continuing immunity. In addition, we found evidence that some normal animals express endogenous levels of natural immunity against neoplasms induced by these viruses and/or against the viruses themselves.

Avian sarcoma virus (ASV)-induced tumor cells that are derived from regressing neoplasms contain about 75% less pp60src kinase activity than do progressively-growing tumor cells. Paradoxically, the polyadenylated RNAs extracted from ‘regressor’ cells found in regressing neoplasms are much more productive than those from progressively-growing tumors in a reticulocyte lysate in vitro translation system, as determined both by time course and concentration curve studies. Electrophoretic analysis of polypeptides corresponding to known ASV proteins further suggests that the translation product from the mRNAs of regressing tumor cells contains much more viral protein than does that derived from progressively-growing sarcoma cells. The identity of two of these viral proteins was confirmed by immunoprecipitation of the respective translation products, using a tumor-bearing rabbit serum with specificity for pp60src and Pr76gag precursor polypeptides, and showed that much more of pp60src and Pr76gag were produced by the mRNAs from regressor than from progressor cells. We further found that ASV genes including genomic and subgenomic species (8.6, 5.0 and 3.2 kb) were present in greater amounts in regressing as opposed to progressively-growing tumor cells. These results support the notion that viral RNAs are accumulated in ‘regressor’ tumor cells.

Herpes simplex viruses (HSV) are able to prevent the lectin-driven mitogenesis of coincubated human peripheral blood lymphocytes. This abrogation of responsiveness is independent of infection and can be obtained by using ultraviolet-inactivated as well as live virus particles. Lymphocytes from patients prone to frequent recurrences of HSV-induced lesions were more susceptible to inhibition of proliferative responsiveness than were cells from either individuals seronegative for HSV type 1 and HSV type 2 or individuals subject only to infrequent recurrences of HSV-induced disease. Lymphocytes from all patients tested were more susceptible to viral abrogation of mitogen responsiveness during preepisodic and acute as opposed to convalescent and postepisodic periods. When exogenous T cell growth factor was added to lymphoid cell cultures that had been coincubated with HSV, the cells were generally able to overcome the inhibition of responsiveness that would otherwise occur. However, this restoration of responsiveness occurred less efficiently in cells from patients with acute HSV-induced lesions and in cells from patients with frequent recurrences of lesions.

The immunotherapeutic effects of the methanol extraction residue (MER) of BCG were investigated in strain 2 guinea pigs injected with cells of the transplantable, diethylnitrosamine-induced, line 10 hepatocarcinoma. MER was more effective in mediating tumour regression in guinea pigs obtained from the Weizmann Institute of Science, Rehovot, Israel than in animals obtained from the National Institutes of Health. Repeated skin testing with solubilized tumour antigen of MER-treated animals whose tumours had regressed led to recurrent tumour growth and/or susceptibility to rechallenge in six of nine guinea pigs so treated. These results suggest the existence of minimal residual disease even in animals which respond positively to immunotherapy.

Resistance to line-10 hepatocarcinoma was studied in the newborn offspring of inbred strain-2 Sewall Wright guinea pigs that had recovered from this tumor after prior administration of subcellular components of Mycobacterium bovis strain BCG. These mothers gave birth to 15 offspring, 53% of which resisted repeated challenges with this tumor. Offspring of mothers who had been given only BCG components were similarly tested. Complete protection was observed in 23.5% of 17 babies and attenuation of disease in many others. All control offspring from normal, untreated mothers succumbed to this tumor. Resistance was associated with delayed cutaneous hypersensitivity reactions to tumor and mycobacterial antigens.

Using a standard radio-receptor assay, we have demonstrated that [125I]insulin can bind specifically to each of two types of purified enveloped viruses, influenza A virus and Rous sarcoma virus. A non-enveloped icosahedral virus (echovirus 11) and herpes simplex virus type 2, which acquires its envelope from the nuclear membrane of the cell, did not possess insulin receptor activity. Displacement of specifically bound radiolabelled insulin from the viral surface was achieved by addition of an excess of unlabelled insulin but not by addition of another unrelated protein, cytochrome C. We conclude that certain types of enveloped viruses may acquire insulin binding sites from the plasma membrane of their host cell.

We have examined 3 different EBV-carrying B cell lines, in terms of ability to be super-infected by the human immunodeficiency virus (HIV-1), and have followed these lines, after infection by HIV-1, over a period of 3 months. We found significant variation among different HIV-1 strains in terms of the multiplicity of infection required to initiate infection in these EBV-positive cell lines. Persistent infection by HIV-1 in the absence of detectable cytopathic effects could be demonstrated, as evaluated by a variety of techniques, including reverse transcriptase assay and immunofluorescence. The results indicate also that all of these cell lines produced progeny HIV-1 intermittently, with large amounts of virus production on some days but not others. In contrast, they were all able to continuously express p24.

A tissue culture system for the growth of human fetal and infantile thymic epithelial (TE) cells has been established and characterized. We have investigated the effects of infection of these cells by human cytomegalovirus (CMV), measles virus, and human immunodeficiency virus type-1 (HIV-1). In the case of CMV, morphological changes were apparent by 2-4 days after viral inoculation of infantile TE cells. CMV-related antigens were detected by immunofluorescence after 12 days, and progeny infectious CMV was recovered from culture media after 18 days. Following infection by measles virus, distinctive, multinucleated giant TE cells appeared in both cultures of fetal and infantile TE cells. Measles virus-inoculated TE cells displayed an altered phenotype, as revealed by reaction with monoclonal antibodies with specificity for a variety of TE markers. Finally, infection of TE cells by HIV-1 resulted in cellular disarrangement, increased numbers of Hassall's corpuscles, and multinucleated giant cells. An increase in the number of cells reactive with monoclonal antibodies, specific for Hassall's corpuscles, was observed in the case of cells infected by either measles virus or HIV-1. These findings suggest that a variety of different viruses can successfully infect thymic epithelial tissue. Because of the important role of the thymus in development of the immune system, it is reasonable to conclude that viral infection of thymic tissue might play an important role in virus-mediated suppression of immune responsiveness.

Chickens bearing tumors which have been induced by avian retroviruses express cellmediated immune responsiveness against antigens which are associated with these neoplasms. We have employed a peripheral lymphocyte stimulation test to characterize antigens which are found in the supernatant fluids of avian retrovirus-infected chicken embryo fibroblast (CEF) cells and in the plasma of birds which have been inoculated with avian myeloblastosis virus (AMV). The results indicated that the antigenic activity being measured was virus group specific, cell transformation independent, and nonvirion in nature. Paradoxically, expression of such antigen(s) was restricted to cells which were actively synthesizing progeny avian retrovirus particles, and was absent in mammalian nonproducer cells which had been transformed by avian sarcoma viruses. Ability to respond immunologically to such antigen(s) was present in animals which had been inoculated with either leukosis or sarcoma viruses. Thymectomy, but not bursectomy, was stimulatory to tumor growth and abolished sensitized lymphocyte immune responsiveness in this system.

How 3'-azido-3'-deoxythymidine (AZT) affects the ability of three different variants of HIV-1 to infect a line of EBV-transformed B cells was studied. Susceptible cells were pretreated with three different concentrations of AZT (1, 5, and 10 microM) for 4 h before viral inoculation and were maintained after infection in drug-containing medium. Establishment of viral infection was assessed by indirect immunofluorescence for viral antigens and by antigen capture assay carried out on culture fluids. AZT completely blocked infection in one of the HIV-1 variants studied; in the other two, treatment of cells with AZT significantly delayed the appearance of progeny virus.

We determined whether drug-resistant variants of HIV-1 could be isolated from the peripheral blood mononuclear cells of 20 individuals with HIV infection (Centers for Disease Control groups II and III) on long-term zidovudine (AZT) therapy. Toward this end, zidovudine (10 microM) has been included in the tissue culture medium used to isolate HIV-1. Under these circumstances, virus with a zidovudine-resistant phenotype was successfully obtained in five out of 20 cases. This property of drug resistance appeared to be stable, and did not disappear upon extended replication of such virus in the absence of drug pressure. Drug-resistant virus could also be isolated from these subjects on subsequent occasions, but was not present in samples obtained prior to therapy. Replication of these zidovudine-resistant isolates in tissue culture was inhibited by each of four other nucleoside analogues. Thus, other drugs may be useful in controlling selective zidovudine-resistant variants of HIV-1.

Restriction factors comprise an important layer of host defense to fight against viral infection. Some restriction factors are constitutively expressed whereas the majority is induced by interferon to elicit innate immunity. In addition to a number of well-characterized interferon-inducible antiviral factors such as RNaseL/OAS, ISG15, Mx, PKR, and ADAR, tetherin (BST-2/CD317/HM1.24) was recently discovered to block the release of enveloped viruses from the cell surface, which is regarded as a novel antiviral mechanism induced by interferon. Here, we briefly review the history of tetherin discovery, discuss how tetherin blocks virus production, and highlight the viral countermeasures to evade tetherin restriction.

The importance of chemokine expression on HIV infection has been emphasized by the discovery that infection of CD4(+) T cells by M-tropic strains of HIV-1 is antagonized by the chemokines RANTES, MIP-1alpha, and MIP-1beta, which are natural ligands of CCR5, a major coreceptor for macrophagetropic (M-tropic) isolates of HIV-1. Similarly, the CCR2b ligands MCP-1 and MCP-3 inhibit productive infection of PBMCs by both CCR5- and CXCR4-dependent strains of HIV-1, suggesting that expression of the MCP-1 chemokine may affect HIV infection via signaling through the CCR2 receptor and subsequent desensitization of the CCR5 and/or CXCR4 signaling pathway. Given the major role played by chemokine receptors in HIV-1 fusion/entry and the regulatory effects of chemokines on HIV-1 infection, we examined the pattern of chemokine gene expression in HIV-1-infected myeloid cells and in primary monocyte/macrophages. Chronic HIV-1 infection of U937 monocytic cells increased the expression of RANTES, MIP-1alpha, MIP-1beta, and IL-8 chemokine genes, but strongly inhibited PMA/PHA- and TNFalpha-induced MCP-1 gene transcription. HIV-1-mediated inhibition of MCP-1 transcription and secretion was further confirmed in de novo HIV-1-infected U937 cells and correlated with a delay in HIV- and signal-induced NF-kappaB binding to the MCP-1 promoter. The inhibition of MCP-1 gene expression may provide a mechanism by which HIV-1 escapes the early influence of chemokine expression in monocytic cells.

Dendritic cells (DC) are among the first targets of human immunodeficiency virus type-1 (HIV-1) infection and in turn play a crucial role in viral transmission to T cells and in the regulation of the immune response. The major group of HIV-1 has diversified genetically based on variation in env sequences and comprise at least 11 subtypes. Because little is known about the host response elicited against different HIV-1 clade isolates in vivo, we sought to use gene expression profiling to identify genes regulated by HIV-1 subtypes B, C, and A/E upon de novo infection of primary immature monocyte-derived DC (iMDDCs). A total of 3700 immune-related genes were subjected to a significance analysis of microarrays (SAM); 656 genes were selected as significant and were further divided into 8 functional categories. Regardless of the time of infection, 20% of the genes affected by HIV-1 were involved in signal transduction, followed by 14% of the genes identified as transcription-related genes, and 7% were classified as playing a role in cell proliferation and cell cycle. Furthermore, 7% of the genes were immune response genes. By 72 h postinfection, genes upregulated by subtype B included the inhibitor of the matrix metalloproteinase TIMP2 and the heat shock protein 40 homolog (Hsp40) DNAJB1, whereas the IFN inducible gene STAT1, the MAPK1/ERK2 kinase regulator ST5, and the chemokine CXCL3 and SHC1 genes were induced by subtypes C and A/E. These analyses distinguish a temporally regulated host response to de novo HIV-1 infection in primary dendritic cells.

BOTH intact bacillus Calmette–Guerin(BCG)1–3 and the methanol extraction residue (MER) fraction4 of BCG have had extensive application in tumour immunotherapy. Treatment with MER nonspecifically stimulates both the cellular and humoral immune systems4,5, and has been successful in tumour immunotherapy in a number of animal models6,7. Experiments in our laboratories, using animals obtained from the Weizmann Institute, Rehovot, Israel, have shown that about 40% of strain 2 guinea pigs injected with MER or with the supernatant of sonically-disrupted BCG (BCG SS), 1–2 months before intradermal inoculation with 106 cells of the transplantable line 10 hepatocarcinoma8,9, are resistant to the growth of this tumour10. Similarly, injection of MER into developing tumour nodules 7d after tumour cell implantation results in complete tumour regression in approximately 40% of the animals tested (M.A.W., P.M. and D.W.W., unpublished).

We have tested the ability of human cytomegalovirus (CMV) to interfere with the interleukin-2 (IL-2)-dependent proliferation of T lymphocytes in long-term tissue culture. The results indicate that CMV was able to establish an apparently abortive infection in approximately 40% of such cells, although productive viral replication could not be detected, and was able to impede cellular proliferation almost completely. The addition of high concentrations of exogenous IL-2 to cultures of CMV co-incubated cells was not readily able to overcome the anti-proliferation inhibitory effect induced by this virus. Exposure to CMV led to an approximate 50% decrease in the number of cells which expressed Tac Ag, or IL-2 receptor, at the cell surface.

Measles virus can replicate in cultures of both infantile and fetal human thymic epithelial cells. Virus-induced cytopathology including syncytium formation was first evident around 24 hr after viral inoculation of these cultures. At the same time, the cultures began to lose their characteristic thymus-like organizational structure. Viral antigens were detected in infected cells by indirect immunofluorescence, and the presence of progeny virions was demonstrated in culture fluids.

Tumor cells which are cultured from the regressor phase of avian sarcoma virus (ASV)-induced tumor growth are deficient with respect to ability to produce progeny transforming virus. In addition, such cells are relatively unreactive with anti-viral antibody and are unable to elaborate, into the medium, antigens which are stimulatory to the sensitized lymphocytes of virus-injected hosts. These deficits can be overcome by treatment of the cells with the tumor promoter, phorbol myristate acetate (PMA).

Summary Peripheral blood lymphocytes of chickens bearing tumours induced by avian sarcoma virus can be specifically stimulated to divide by the crude culture fluids of virus-infected cells. In this communication, we show that relevant antigenic activity apparently resides in each of the internal virus proteins p15 and p27. The ability of infectious culture fluids to be mitogenic for sensitized lymphocytes is greatly reduced following treatment with antibodies specific for either total avian myeloblastosis virus (AMV) protein or for p27.

Summary Tumours induced in chickens by inoculation of avian sarcoma viruses are frequently capable of undergoing spontaneous regression. It is only those tumour cells which have been derived from progressively growing neoplasms that are able to produce transforming progeny virus in vitro and to shed into the culture medium antigens which are specifically reactive with the peripheral lymphocytes of sarcoma-bearing hosts. Following multiple passages and extended growth in culture, however, the ability of these tumour cell fluids to stimulate the lymphocytes of sensitized hosts diminishes in concert with the declining capacity of these cells to continue to synthesize fully transforming progeny virus. In certain instances, however, aged tumour cells are able to synthesize particles which contain the enzyme RNA-dependent DNA polymerase yet lack detectable envelope glycoprotein.

The immunotherapeutic effects of the methanol extraction residue (MER) of BCG were investigated in strain 2 guinea pigs bearing the transplantable line 10 hepatocarcinoma, a tumor originally induced in guinea pigs at the National Institutes of Health (NIH) by ingestion of the carcinogen diethylnitrosamine. MER was more effective in mediating tumor regression in guinea pigs obtained from the Weizmann Institute of Science (WI), Rehovot, Israel, than in animals obtained from the National Institutes of Health (NIH). These differences indicate the dramatic effects which minor histoincompatibilities between cancer cells and animal substrains may have on experimental results, and highlight the need for immunotherapy experiments to be conducted on laboratory tumors grown in their autochthonous hosts. MER was effective only when injected directly into growing tumor nodules and had no effect on tumor development when administered distally. In contrast, all animals which received both MER and tumor cells developed specific cell-mediated anti-tumor immune responsiveness at higher levels than did non-MER-treated tumor-bearing controls as measured by delayed cutaneous hypersensitivity and in vitro lymphocyte reactivity experiments. Furthermore, the results of the latter but not the former studies suggested that guinea pigs which received MER were able to mount such an immune response more rapidly than their non-treated counterparts. This apparent stimulation of anti-tumor immunity was observed in treated animals regardless of substrain or site of MER injection, and could not be correlated with the outcome of immunotherapy.

Infection of a newly described human T lymphoid cell line, CEM-CL10, with three different variants of HIV-1 resulted in cytopathic effects followed by cell lysis. Following primary lytic infection, proviral DNA could not be detected by Southern blot analysis in the outgrowth of the surviving CEM-CL 10 cells 60 days after initial exposure to HIV-1. These surviving cells could be further grown as a separate line, derived from CEM-CL10, and were found to be resistant to subsequent infection by HIV-1. A marked decrease in CD4 antigen expression was observed in these latter cells but not of the CD3 and transferrin receptor antigens. This decline in cell surface CD4 expression was correlated with both an absence of specific CD4 mRNA and with changes in structure of the CD4 gene. Both the HIV-1-sensitive CEM-CL10 cell line and its CD4(-), HIV-1-resistant derivative line, will be made available to interested investigators.

Cytomegalovirus (CMV) has often been cited as a cause of immune suppression in children, yet little is known of the mechanisms through which this agent might affect immune function. We have succeeded in using CMV to productively infect cultured human fetal and infantile thymic epithelial (TE) cells. Morphological changes were apparent by 2–4 days after viral inoculation. CMV-related early antigen (EA) and late antigen (LA) were detected by immunofluorescence after 8 days, and progeny infectious CMV was recovered from culture media after 12–17 days. TE cells that reacted with monoclonal antibodies specific for keratin and for GQ ganglioside were predominant throughout the culture period. In contrast, infection by CMV resulted in a significant decrease in numbers of cells reactive with monoclonal antibodies specific for mesoderm-derived components. Inoculation of TE cells with CMV also caused a diminution in levels of detectable interleukin-1 (IL-1)-related antigen by 17 days after infection.

Several different types of retroviruses are able, when co-incubated with lymphoid cells in the presence of lectins, to impede the lymphocyte blastogenesis response that normally ensues. Such inhibition of responsiveness can be obtained using UV-inactivated as well as live virus and appears to be the result of structural interactions between macrophages in the cell population and the viral surface. Cultures which contain each of T cell mitogens and virus have sub-normal levels of the lymphokine T cell growth factor (TCGF). The addition to such cultures of exogenous TCGF causes a concentration-dependent reversal of the virus-mediated inhibitory effect.