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Persistent infection of cells in culture by measles virus. I. Development and characteristics of HeLa sublines persistently infected with complete virus.

Rustigian, Robert (Tufts University School of Medicine, Boston, Mass.). Persistent infection of cells in culture by measles virus. I. Development and characteristics of HeLa sublines persistently infected with complete virus. J. Bacteriol. 92:1792-1804. 1966.-After the development of marked cytopathic effects in HeLa cultures infected with the Edmonston strain of measles virus, renewed cell growth occurred, and HeLa sublines persistently infected with measles virus were obtained. Persistent infection has occurred in a large fraction of the cells of infected clonal lines for more than 300 to 500 cell generations during a period of 6 years. One mechanism by means of which infection was maintained in the clonal lines is transmission of virus or viral subunits from cell to cell at division. Continued subculture of the persistently infected populations resulted in the virtual disappearance of cytopathic effects, a marked decrease in the amount of extracellular virus, and alterations in the cytopathogenicity of virus recovered from persistently infected populations. The intracellular virus-host cell events in late passages of the infected clonal lines appeared to be similar to those in cells of primary infected cultures at early stages of infection, as judged by the pattern of viral immunofluorescence and the very low incidence of cells with intranuclear inclusion bodies. Cultures of the persistently infected clonal lines were highly resistant to super infection by parent Edmonston virus. Cultures of one of these clonal lines were just as susceptible as normal HeLa cultures to vaccinia, herpes simplex, and polio type 2 viruses, and a simian agent, with a possible low degree of resistance to the simian agent.

Antigens↗

Analysis of Aleutian disease virus infection in vitro and in vivo: demonstration of Aleutian disease virus DNA in tissues of infected mink.

Aleutian disease virus (ADV) infection was analyzed in vivo and in vitro to compare virus replication in cell culture and in mink. Initial experiments compared cultures of Crandell feline kidney (CRFK) cells infected with the avirulent ADV-G strain or the highly virulent Utah I ADV. The number of ADV-infected cells was estimated by calculating the percentage of cells displaying ADV antigen by immunofluorescence (IFA), and several parameters of infection were determined. Infected cells contained large quantities of viral DNA (more than 10(5) genomes per infected cell) as estimated by dot-blot DNA-DNA hybridization, and much of the viral DNA, when analyzed by Southern blot hybridization, was found to be of a 4.8-kilobase-pair duplex monomeric replicative form (DM DNA). Furthermore, the cultures contained 7 to 67 fluorescence-forming units (FFU) per infected cell, and the ADV genome per FFU ratio ranged between 2 X 10(3) and 164 X 10(3). Finally, the pattern of viral antigen detected by IFA was characteristically nuclear, although cytoplasmic fluorescence was often found in the same cells. Because no difference was noted between the two virus strains when cultures containing similar numbers of infected cells were compared, it seemed that both viruses behaved similarly in infected cell culture. These data were used as a basis for the analysis of infection of mink by virulent Utah I ADV. Ten days after infection, the highest levels of viral DNA were detected in spleen (373 genomes per cell), mesenteric lymph node (MLN; 750 genomes per cell), and liver (373 genomes per cell). In marked contrast to infected CRFK cells, the predominant species of ADV DNA in all tissues was single-stranded virion DNA; however, 4.8-kilobase-pair DM DNA was found in MLN and spleen. This observation suggested that MLN and spleen were sites of virus replication, but that the DNA found in liver reflected sequestration of virus produced elsewhere. A final set of experiments examined MLN taken from nine mink 10 days after Utah I ADV infection. All of the nodes contained ADV DNA (46 to 750 genomes per cell), and although single-stranded virion DNA was always the most abundant species, DM DNA was observed. All of the lymph nodes contained virus infectious for CRFK cells, but when the genome per FFU ratio was calculated, virus from the lymph nodes required almost 1,000 times more genomes to produce an FFU than did virus prepared from infected cell cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

Aleutian Mink Disease↗

Mechanisms of nonrandom human immunodeficiency virus type 1 infection and double infection: preference in virus entry is important but is not the sole factor.

We previously demonstrated that human immunodeficiency virus type 1 (HIV-1) infection is nonrandom and that double infection occurs more frequently than predicted from random events. To probe the possible mechanisms for nonrandom infection, we examined the role of HIV-1 entry pathways by using viruses pseudotyped with either CCR5-tropic HIV-1 Env or vesicular stomatitis virus G protein (VSV G). These two proteins use different receptors and entry pathways. We found that regardless of the protein used, double infection occurred more frequently than random events, indicating nonrandom HIV-1 infection in both entry pathways. However, the frequency of double infection differed significantly, depending on the envelope protein. In primary CD4(+) T cells, double infection occurred most frequently when both viruses had CCR5-tropic HIV-1 Env and least frequently when the two viruses had different envelopes. These results indicated that the preference in virus entry was a significant but not the only factor contributing to nonrandom double infection. Furthermore, we demonstrated that the CD4 expression level in primary T cells affects their susceptibility to CCR5-tropic HIV-1 infection but not VSV G-pseudotyped HIV-1 infection. We have also examined infection with two viruses pseudotyped with CCR5- or CXCR4-tropic HIV-1 Env and have found that double infection occurred more frequently than random events. These results indicate that coreceptor usage is not a barrier to recombination between the two virus populations. In our previous study, we also demonstrated nonrandom double infection via dendritic cell (DC)-mediated HIV-1 transmission. To test our hypothesis that multiple HIV-1 virions are transmitted during DC-T-cell contact, we used two populations of DCs, each capturing one vector virus, and added both DC populations to T cells. We observed a decreased frequency of double infection compared with experiments in which DCs captured both viruses simultaneously. Therefore, these results support our hypothesis that multiple virions are transmitted from DCs to T cells during cell-mediated HIV-1 transmission.

CD4 Antigens↗

Porcine reproductive and respiratory syndrome virus (PRRSV) infection spreads by cell-to-cell transfer in cultured MARC-145 cells, is dependent on an intact cytoskeleton, and is suppressed by drug-targeting of cell permissiveness to virus infection.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiologic agent of PRRS, causing widespread chronic infections which are largely uncontrolled by currently available vaccines or other antiviral measures. Cultured monkey kidney (MARC-145) cells provide an important tool for the study of PRRSV replication. For the present study, flow cytometric and fluorescence antibody (FA) analyses of PRRSV infection of cultured MARC-145 cells were carried out in experiments designed to clarify viral dynamics and the mechanism of viral spread. The roles of viral permissiveness and the cytoskeleton in PRRSV infection and transmission were examined in conjunction with antiviral and cytotoxic drugs. RESULTS: Flow cytometric and FA analyses of PRRSV antigen expression revealed distinct primary and secondary phases of MARC-145 cell infection. PRRSV antigen was randomly expressed in a few percent of cells during the primary phase of infection (up to about 20-22 h p.i.), but the logarithmic infection phase (days 2-3 p.i.), was characterized by secondary spread to clusters of infected cells. The formation of secondary clusters of PRRSV-infected cells preceded the development of CPE in MARC-145 cells, and both primary and secondary PRRSV infection were inhibited by colchicine and cytochalasin D, demonstrating a critical role of the cytoskeleton in viral permissiveness as well as cell-to-cell transmission from a subpopulation of cells permissive for free virus to secondary targets. Cellular expression of actin also appeared to correlate with PRRSV resistance, suggesting a second role of the actin cytoskeleton as a potential barrier to cell-to-cell transmission. PRRSV infection and cell-to-cell transmission were efficiently suppressed by interferon-gamma (IFN-gamma), as well as the more-potent experimental antiviral agent AK-2. CONCLUSION: The results demonstrate two distinct mechanisms of PRRSV infection: primary infection of a relatively small subpopulation of innately PRRSV-permissive cells, and secondary cell-to-cell transmission to contiguous cells which appear non-permissive to free virus. The results also indicate that an intact cytoskeleton is critical for PRRSV infection, and that viral permissiveness is a highly efficient drug target to control PRRSV infection. The data from this experimental system have important implications for the mechanisms of PRRSV persistence and pathology, as well as for a better understanding of arterivirus regulation.

Animals↗

TT virus infection in human immunodeficiency virus type 1 infected mothers and their infants.

Serum TT virus (TTV) DNA was determined in 83 human immunodeficiency virus type 1 (HIV 1) infected mothers [46 intravenous drug user and 37 non-intravenous drug user women] and their infants. Twenty-nine (34.9%) mothers were TTV infected. Infection was more frequent among intravenous drug user than non-intravenous drug user mothers [21/46 (45.6%) vs. 8/37 (21.6%); relative risk (RR): 2.1; 95% confidence limits (95% CL): 1.1-4.2; P = 0.023] and among intravenous drug users who carried on injecting than in those who had given it up [10/14 (71.4%) vs. 11/32 (34.3%); RR: 2.1 (95%CL: 1.2-3.7); P = 0. 021]. Infection was not related to age, CD4-positive T-lymphocyte counts, HIV 1 load, hepatitis B (HBV), G/GB-C (GBV-C/HGV), C (HCV) virus exposure. Eight (27.5%) infants born to TTV infected (but none of those born to TTV uninfected) mothers were TTV infected at a median age of 1.5 (range: 0.6-2.8) months. Infants born by vaginal/emergency caesarean delivery were more frequently infected than those born by elective caesarean delivery [7/16 (43.7%) vs. 1/13 (7.6%); RR: 2.1; 95%CL: 1.2-3.5; P = 0.033]. Infection in infants was not related to maternal CD4-positive T-lymphocyte counts, HIV 1 load, and HIV 1, HBV, GBV-C/HGV, or HCV transmission. No infant became TTV infected thereafter. No TTV infected child [follow-up: 31 (median; range: 6-60) months] showed signs of liver disease; five infants cleared TTV DNA after 22 (median; range: 6-60) months. TTV infection in HIV 1 infected women is prevalently related to intravenous drug user. The findings suggest that infants may acquire TTV at birth. Infection may persist without evident liver disease.

Adolescent↗

Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection.

BACKGROUND: Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable. OBJECTIVES: To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection. SEARCH STRATEGY: The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity 2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999. 4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS 5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched. SELECTION CRITERIA: Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models. MAIN RESULTS: Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). (ABSTRACT TRUNCATED)

Anti-HIV Agents↗

PC-Fix and local infection resistance--influence of implant design on postoperative infection development, clinical and experimental results.

Bacterial infection is still one of the main complications after internal fixation of fractures. The design of implants influences local infection resistance. To reduce the development of infections around implants after internal fixation, the vitality of the bone should be preserved to optimize cellular and humoral host defence mechanisms. For extramedullary fracture fixation, two implant designs are currently in routine use: the Dynamic Compression Plate (DCP) and the Limited Contact Dynamic Compression Plate (LC-DCP). The Point-Contact-Fixator (PC-Fix) is a new design concept based on the philosophy of the LC-DCP and the external fixator. Its function relies on splinting the fragments of a fracture internally with locking bolts rather than with screws that compress the plate to the bone. In this way, the blood supply is not compromised by compression of the periosteum. We investigated the effect of this new design on the incidence of postoperative infection rates in a clinical and an experimental setting. In a prospective multicentre study 1,229 PC-Fixators were used in 896 patients. Of these, 1,172 were available for assessment of infection development. The overall infection rate was 1.1% (13/1,172). The infection rate after open fractures was 1.6% (4/256) and after closed procedures (including closed fractures, osteotomies and non-unions) 1.0% (9/916). These rates are low in comparison to published rates using DCP and LC-DCP. In an experimental study, we compared the infection rates across two groups of rabbits four weeks after fixing either a bacterially contaminated DCP or a PC-Fix to the tibia. Infection rates in the DCP group were significantly higher than in the PC-Fix group: Of the 38 evaluated animals, 12 with a DCP and 5 with a PC-Fix developed local infection (p=0.022). The new PC-Fix design shows low postoperative infection rates in the clinical setting and lower infection rates than the DCP in the experimental setting. The design is an important step in the process of reducing postoperative infection rates.

Adolescent↗

Latent infection as a source of disseminated disease caused by organisms of the Mycobacterium avium complex in simian immunodeficiency virus-infected rhesus macaques.

Whether infection with Mycobacterium avium complex (MAC) among patients with acquired immune deficiency syndrome results from recent exposure to virulent strains or reactivation of latent infection acquired years earlier is unknown. To address this question, tissue samples from 47 simian immunodeficiency virus (SIV)-infected and 63 SIV-uninfected rhesus macaques were cultured. MAC was cultured from 14 SIV-uninfected macaques (22.2%) and 32 SIV-infected macaques (68.1%); median bacterial burdens were 33.3 and 998.7 cfu/g, respectively. Genetically distinct strains of MAC were identified for 13 SIV-uninfected macaques (20.6%) and 15 SIV-infected macaques (31.9%). A genetically identical MAC strain (K128A) was identified for 25 SIV-infected macaques (53.2%) and 1 SIV-uninfected macaque (1.6%). Multivariate analysis identified infection with SIV/Delta(B670), diagnosis of an SIV-related tumor or opportunistic infection, and birth on site as risks for MAC infection. SIV-uninfected and SIV-infected macaques yielding unique strains of MAC were considered to have latent and reactivation infection, respectively, whereas animals infected with strain K128A were considered to have recent infection, demonstrating that both mechanisms occur among rhesus macaques.

Animals↗

How do viral infections predispose patients to bacterial infections?

PURPOSE OF REVIEW: Bacterial sepsis is a leading cause of death in the United States, accounting for over 200,000 fatalities annually. Approximately half of bacterial sepsis cases occur following acute respiratory infections, and the lungs are the most common organs to fail. Notably, outbreaks of respiratory viral infections are associated with an increased incidence or severity of bacterial co-infections, with normally innocuous infections often becoming fatal. Understanding the 'lethal synergism' associated with concomitant infections may point the way toward improved anti-sepsis treatments. RECENT FINDINGS: Murine models of viral and bacterial co-infection mimic the lethal synergism observed in humans and reveal at least two mechanisms of interaction. First, bacterial infiltration is heightened during acute viral infection. Secondly, the nature of responding cell populations is dramatically altered during concomitant infections. Although natural killer cells and macrophages are predominant cell populations responding to bacterial infection in a naïve host, there is also a large T cell component that is activated upon viral infection. Inflammatory cytokines produced by these cells contribute to lethal immunopathology, and therapeutic strategies need to target the initial causative microbes as well as subsequent inflammatory responses. Current therapies directed only at the host immune response have not been overly successful, owing largely to difficulties in reversing the severe immunopathology associated with sepsis. SUMMARY: Respiratory viral infections may facilitate secondary bacterial infections and increase host immunopathology through the overproduction of inflammatory cytokines. Preventive measures, including vaccination and aggressive antimicrobial therapy early in the course of infection, may significantly reduce the morbidity and mortality of sepsis.

Animals↗

Nosocomial infections in HIV infected patients. Gruppo HIV e Infezioni Ospedaliere.

OBJECTIVES: To determine the incidence of nosocomial infections (NI) in HIV-infected patients and to analyse some of the associated risk factors. DESIGN AND SETTING: Multicentre prospective study on consecutive HIV-infected patients admitted to 19 Italian acute-care infectious disease wards. METHODS: All patients admitted during a 1-year period were followed-up for NI until their discharge. Univariate and multivariate analyses were performed for NI risk factors. RESULTS: As of June 1998 a total of 344 NI occurred in 4330 admissions, with at least one NI in 273 admissions (6.3%). The incidence rate of NI was 3.6 per 1000 patient days [95% confidence interval (CI), 3.2-4.1]. Overall distribution by site was 36.6% bloodstream infections (BSI), 30.5% urinary tract infections, 18.4% pneumonia, 5.2% skin/soft tissue infections, 2.0% surgical wound infections and 7.3% others. Fifty-five out of the 126 BSI were related to a central venous catheter (CVC); the rate of CVC-associated infections was eight infections per 1000 devices. At multivariate analysis, variables independently associated with NI included CD4 T-lymphocyte count < 200 x 10(6)/l [odds ratio (OR), 2.21; 95% CI, 1.35-3.62], Karnofsky Performance Status < 40 (OR, 1.89; 95% CI, 1.28-2.78), therapy with corticosteroids (OR, 1.78; 95% CI, 1.29-2.45), CVC (OR, 3.24; 95% CI, 2.41-4.35), urinary catheter (OR, 6.53; 95% CI, 4.81-8.86) and surgery (OR, 3.13; 95% CI, 1.90-5.15). CONCLUSIONS: Results suggest that NI occur commonly in HIV-infected patients. As the number of cases of HIV continues to increase, the number of HIV-infected patients requiring hospitalization may also increase. Clinicians need to be aware of the risk factors for NI and must consider these infections in the overall management of HIV-infected, hospitalized patients.

AIDS-Related Opportunistic Infections↗

Secondary infections of AIDS autopsy cases in Japan with special emphasis on Mycobacterium avium-intracellulare complex infection.

In order to study the frequency of secondary infections of AIDS autopsy cases in Japan, especially the frequency of Mycobacterium aviumintracellulare complex (MAC) infection, retrospective autopsy study was conducted between 1986 and 1997 at the affiliated hospital of Institute of Medical Sciences, University of Tokyo. Secondary infections of various organs from 43 AIDS autopsy cases were examined using histopathology, genetic diagnosis of tuberculosis, Ziehl-Neelsen stain for acid-fast bacilli and immunohistochemistry. Nontuberculous mycobacterial infection (Mycobacterium avium) was observed in 17 cases (40%) out of 43 using polymerase chain reaction (PCR), but M. tuberculosis infection was not observed. Ziehl-Neelsen staining showed a positive reaction in lung and spleen tissues of 7 AIDS autopsy cases. Immunohistochemistry using anti-BCG antibody revealed positivity in 7 AIDS autopsy cases. CD4 counts of 17 AIDS patients with mycobacterial infection were less than 18.7/microl. Other opportunistic infections were also examined by histopathology. Secondary infections were present in every case, and these included cytomegalovirus infection (32 cases), Pneumocystis carinii (15 cases), Candida (16 cases), Aspergillus (12 cases), Cryptococcus (6 cases), Toxoplasma (6 cases), methicillin-resistant Staphylococcus aureus (3 cases), herpes virus (1 case) and Entamoeba histolytica (1 case). Malignant lymphoma was recognized in 14 cases and Kaposi's sarcoma in 6. This is the systemic report on secondary infections of AIDS autopsy cases in Japan. In diagnosis of mycobacterial infections, PCR was more useful than staining for acid-fast bacilli and immunohistochemistry. Secondary infections (especially mycobacterial infection) were closely associated with the low CD4 count.

AIDS-Related Opportunistic Infections↗

Management of chronic hepatitis C in HIV-co-infected patients--results from the First International Workshop on HIV and Hepatitis Co-infection, 2nd-4th December 2004, Amsterdam, Netherlands.

About 30% of HIV-positive individuals are concomitantly infected with HCV within the United States and Europe. Approximately 50 to 90 % of persons who acquired HIV from injecting drugs are co-infected with HCV. In these dually infected individuals the presence of each viral infection may impact the natural course of the other one, and worsening of associated liver disease and complications within this population are frequent. The management of chronic hepatitis C (cHC) in HCV-HIV-co-infection has become a major challenge, as possible interactions with antiretroviral therapy (ART), increased risk of special side effects, as well as compromises in adherence of patients, who already take several drugs, have to be taken into account. Treatment strategies to fight HCV-infection have been essentially ameliorated during the past three years in using pegylated interferon alpha (PegIFN alpha) combined with ribavirin (Rbv). There is hope that the beneficial therapeutic outcome in HCV-mono-infected individuals may be at least partly translated into successful treatment of dually infected patients too. However, the stepwise amelioration of therapeutic options and strategies does actually not yet result in equal anti-HCV response rates for co-infected compared to HCV-mono-infected persons. The 1st International Workshop on HIV and Hepatitis Co-infection 2004, was initiated to face the severe clinical problems which arise from viral hepatitis and HIV dual infection. The organising committee was headed by J. K. Rockstroh, University of Bonn, Germany, as chair and M. Sulkowski, John Hopkins University, USA, as co-chair of the meeting, in which more than 300 researchers and physicians from various European and US locations participated. This report summarizes some results on epidemiology, pathogenesis, viral interactions, and treatment of chronic hepatitis C in HIV-infected individuals.

AIDS-Related Opportunistic Infections↗

The risk of transmission of genital Chlamydia trachomatis infection is less than that of genital Neisseria gonorrhoeae infection.

A total of 211 men with 237 female sexual partners and a total of 155 women with 156 male consorts were examined for genital infection with Chlamydia trachomatis and Neisseria gonorrhoeae. The index patients had either single chlamydial or gonococcal infections or dual infections with both microorganisms. Analysis of recovery rates for groups of sexual consorts indicated that gonorrhea was contracted more frequently than chlamydial infection. Thus, when index patients had dual infections, 45% and 28% of their female and male consorts, respectively, had chlamydial infection, but 64% and 77%, respectively, had gonorrhea. When index patients had single infections with C. trachomatis or N. gonorrhoeae, chlamydial infections were observed in consorts of 45% (women) and 28% (men), but gonococcal infections were observed in 80% (women) and 81% (men). Moreover, a significantly larger proportion of consorts of patients with chlamydial infection eluded infection than did partners of patients with gonorrhea. Women who used an intrauterine contraceptive device had chlamydial and gonococcal infections more often than those who used other forms of contraception, or no contraceptive.

Adolescent↗

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents: retention of naive T lymphocytes in HIV-infected adolescents. The Adolescent Medicine HIV/AIDS Research Network.

BACKGROUND: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. OBJECTIVE: To assess lymphocyte subsets in HIV-infected and high-risk HIV-negative adolescents. DESIGN: The Reaching for Excellence in Adolescent Care and Health Project of the Adolescent Medicine HIV/AIDS Research Network recruits a cohort of HIV-infected and high-risk HIV-uninfected adolescents, aged 13 to 18 years 364 days, into a study of biomedical and behavioral features of HIV infection as seen in the context of full availability of primary care and HIV-related consultative services. Lymphocyte phenotypes were determined using standard 3-color flow cytometry. SETTING: The Reaching for Excellence in Adolescent Care and Health Project is carried out at 16 clinical sites in 14 urban areas. PARTICIPANTS: T-lymphocyte subsets are reported in 192 HIV-positive and 78 HIV-negative youths. RESULTS: For HIV-positive subjects, the total CD4+ cell count and the percentage of CD4+ cells are decreased when compared with those of the HIV-negative controls (P<.001). The reduction in total CD4+ cells reflects a loss of naive, and memory, CD4+ cells compared with HIV-negative youths. Human immunodeficiency virus-infected adolescents, many of whom have been infected recently (ie, those with CD4+ cell counts > or =0.500 x 10(9)/L [500/microL]), have a significant increase in naive CD8+ cells compared with HIV-negative youths (P<.01). There also is a significant increase in memory CD8+ cells at all strata of total CD4+ cells compared with HIV-negative youths (P<.01). The increase in naive CD8+ cells in those subjects with CD4+ cell counts of 0.500 x 10(9)/L or greater is a unique finding in this cohort. CONCLUSIONS: This study demonstrates high levels of naive CD8+ cells in response to HIV infection in adolescents with CD4+ cell counts of 0.500 X 10(9)/L or greater. The presence of high levels of naive CD8+ cells suggests functioning thymic tissue in some adolescents infected with HIV. Furthermore, the normal level of naive CD4+ cells in adolescents with CD4+ levels of 0.500 x 10(9)/L or greater provides additional support for the concept of a more robust immune system in HIV-infected adolescents compared with HIV-infected adults. These observations suggest that the immune system of HIV-infected adolescents may be capable of better responses to neoantigens and cytotoxic T-lymphocyte responses to HIV than the immune system of infected children or adults. Human immunodeficiency virus-infected adolescents may have an immune system that is capable of reconstitution following highly active antiretroviral therapy.

Adolescent↗

Tuberculosis in human immunodeficiency virus-infected children. A family infection.

OBJECTIVE: To study the epidemiologic and clinical features of infection with Mycobacterium tuberculosis in human immunodeficiency virus (HIV)-infected children and their families. PATIENTS AND CLINICAL SETTING: Sixty families of children with HIV infection, children of HIV indeterminate status, and seroreverters underwent follow-up in a comprehensive multidisciplinary program for children and families. METHODS: Infection with M tuberculosis was diagnosed based on a positive Mantoux test result or a positive culture. RESULTS: Mycobacterium tuberculosis infection was diagnosed in seven children (three infected with HIV, three seroreverters, and one uninfected sibling of an infected child) from four families (6%). All infections were detected in the period from March 1990 through January 1992. Six of seven children had a history of exposure to M tuberculosis in an HIV-infected adult (parent) who was an intravenous drug user, homeless, and/or noncompliant with the medical regimen. All HIV-infected children and one seroreverter had pulmonary tuberculosis. One child died of complications of tuberculosis and HIV infection. The M tuberculosis isolated from this child was resistant to isoniazid, rifampin, and streptomycin sulfate. CONCLUSIONS: Tuberculosis is a growing problem among inner-city children born to HIV-infected parents. Children infected with HIV in this study had symptomatic and severe disease with tuberculosis, which reflected the drug susceptibility pattern of M tuberculosis seen in our community.

AIDS-Related Opportunistic Infections↗

Infection build-up and development of immunity in calves following primary Dictyocaulus viviparus infections of different levels at the beginning or in the middle of the grazing season.

An experiment was carried out to study the build-up of infection and development of immunity against Dictyocaulus viviparus infections in calves. Six groups of four calves were used. Groups 1-5 grazed on separate pastures and Group 6 served as a permanently housed control group. To simulate 'low' and 'very low' overwintered pasture infectivity, Groups 1 and 2 were infected experimentally six times with ten and two larvae, respectively, during the first 3 weeks on pasture in May. From the middle of July, Groups 2-4 were experimentally infected six times in 3 weeks with 10, 10 and 100 larvae, respectively, to simulate 'low' and 'moderate' pasture contamination by carriers. Group 5 served as a non-infected pasture control group. After housing of Groups 1-5 in October, all calves were treated with oxfendazole and challenged with 5000 larvae of D. viviparus to evaluate the development of immunity. The results showed a similar population build-up of lungworm infections in Groups 1-4. After the beginning of patency, 24-35 days after primary infection, an increase in faecal larval counts occurred 31-35 days later as a result of re-infection. For Group 2, this was only true when the infections with a total of 12 larvae in May were ignored, as these did not result in patent infections. Faecal larval counts were highest in Group 4, which was the only group with mild signs of lungworm disease occurring in the re-infection period. The worm counts at necropsy showed the development of immunity in Groups 1-4 but not in Group 5. This is consistent with the fact that Group 5 did not develop patent lungworm infections throughout the grazing season.

Animals↗

Effect of teat skin disinfection on the rate of infection and interval to infection in cows exposed to high levels of Staphylococcus aureus.

All teats of a herd of lactating cows were contaminated after each milking with Staphylococcus aureus. Two teats of each cow were subsequently dipped in an iodine solution, while the remaining 2 teats were not dipped. For cows with a single infection the interval to infection in dipped and undipped quarters was 64 and 60 d respectively, while for the first infected quarter of cows with multiple infections the interval to infection in dipped and undipped quarters was 50 and 39 d respectively. For the second quarter infected in cows with multiple infections, the period between the first and second infection was 21 and 12 d for dipped and undipped quarters respectively. It is suggested that while teat skin disinfection was effective in reducing the rate of new infection, it had little effect on the process of infection in those quarters becoming infected. The occurrence of an infection in one quarter doubled the rate of infection in the other quarters.

Animals↗

Beneficial effect of Salmonella typhimurium infection and of immunoglobulins from S. typhimurium-infected mice on the autoimmune disease of (NZB x NZW) F1 mice.

Various infections can precede or aggravate autoimmune diseases. Yet a beneficial effect of infection has also been described an various mechanisms have been postulated to explain this effect. The aim of this study was to examine the hypothesis that infection can have an immunoregulatory effect on the autoimmune process via the increased production of natural polyreactive antibodies. The effect of Salmonella typhimurium infection on the lupus-like disease of (NZB x NZW)F1 (B/W) mice was therefore studied. The effect of IgM and IgG preparations isolated from the serum of S. typhimurium-infected C57B1/6 and CBA mice on the autoimmune disease of B/W mice was also tested. C57B1/6 and CBA mice were chosen because they are respectively genetically susceptible and resistant to S. typhimurium infection and they differ in their antibody response during the early phase of infection. CBA mice can mount a specific anti-bacterium antibody response, whereas C57B1/6 mice present increased production of polyreactive antibodies. The infection effect was evaluated on several disease parameters, i.e. survival, incidence of high grade proteinuria and serum IgM and IgG antibody activity directed against a panel of autoantigens. Our main findings were: (i) infection of B/W mice with an attenuated strain of S. typhimurium delayed the course of the autoimmune disease when performed before the appearance of autoimmune symptoms; and (ii) IgM and IgG preparations from S. typhimurium-infected C57B1/6 mice had a similar effect whereas the IgM and IgG preparations from infected CBA mice, as well as from normal C57B1/6 and CBA mice, were ineffective. These results suggest that S. typhimurium infection can beneficially influence the development of the autoimmune disease of B/W mice. The immunoregulatory effect of the infection seems to be related at least partially, to the increase of a particular population of antibodies, the polyreactive antibodies.

Animals↗