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Seroepidemiologic surveys conducted in Africa have demonstrated infection with HIV-2 in most West African nations surveyed. There appears to be little overlap with geographic regions reporting high rates of HIV-1 infection and AIDS. Seroprevalence for HIV-2 is 2-8 fold higher in sexually active groups demonstrating that similar to HIV-1 this virus is also sexually transmitted. Although high rates of HIV-2 infection can be seen in some West African populations the number of AIDS cases is still quite low suggesting a distinct pathobiology to this new human retrovirus. Cohort studies of HIV-2 infected individuals have also failed to demonstrate progression to clinical symptomatology associated with AIDS in an African setting. Keywords: Immunosuppression; Viruses; Serology; Epidemiology; Virus diseases.

The following report describes the methods used to produce human and primate immune globulin to Lassa fever and Argentinian hemorrhagic fever viruses and the results of the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) testing of these products. Each preparation has viral neutralizing activity and is a safe, stable, well tolerated solution suitable for intravenous injection. Included also are the experiments to demonstrate the ability of the above methods to remove Human Immunodeficiency Virus (HIV) from the raw plasma. Keywords: Areavirus; Hemorrhagic fevers; Immune plasma; Lassa fever; Immunotherapy; RA I; Antibodies; Human Immunodeficiency viruses.

A systematic viral isolation study has been performed on peripheral blood lymphocytes obtained from Air Force personnel positive for antibodies to the human immunodeficiency virus (HIV-1) as assessed by HIV-ELISA and/or immunoblot assays. The co-culture technique employed for viral isolation involves admixing with PHA-activated PBL from normal donors as target cells in the presence of interleukin 2 (IL-2). Assays to determine reverse transcriptase cells (RT) activity in the culture supernatants were used to detect productive viral infectivity in vitro. RT-negative samples were further tested for the presence of HIV-p24 antigen. The results of this viral isolation study in combination with neurological, clinical, and immunological manifestations assessed by the Wilford Hall USAF Medical Center personnel should contribute to our increased understanding of the natural history of the acquired immunodeficiency syndrome. Keywords: Human immunodeficiency virus; Viral isolation; Co-culture; Reverse transcriptase; p24 Antigen capture assay; RA 1.

This editorial points out the different purposes for Center For Disease Control (CDC) case definition and the Walter Reed (WR) staging classification of HIV infection. CDC classification having a primarily epidemiological and public health bias while WR classification a prognostic and severity of illness indicator for a specific patient. Authors agree with Dr. Justice who wants a classification system for patients with end stage disease, but believe her system fall short in four areas, 1) use of CDC definition as starting place, 2) possibility of biased patient population as basis, 3) use of broad measures of physiologic deficits, 4) inability of system to predict survivability of end stage patients. Keywords: Acquired immunodeficiency syndrome; Human immunodeficiency virus; Disease stages; Human immunodeficiency virus infection. Reprints., Pub. in the New England Jnl. of Medicine, v320 p1414-1416, 25 May 1989.

The acquired immune deficiency syndrome (AIDS) is the clinically apparent preterminal stage of the prolonged infection with the human immunodeficiency virus (HIV), most often manifested as Pneumocystis carinii pneumonia, Kaposi's sarcoma, or other opportunistic infections or malignancies. AIDS is by definition a clinical syndrome diagnosis. This article deals exclusively with the diagnosis of HIV infection, not with AIDS, and reflects the author's belief that quality medical care demands a precise etiologic diagnosis. A United States Presidential Commission recently stated that 'The term AIDS is obsolete.' Nowhere is this more true than in the diagnostic laboratory. Keywords: Diagnosis medicine; Diagnosis of HIV; Human immunodeficiency virus; AIDS diagnosis; Laboratory diagnosis of HIV; Reprints., Published in Clinics in Laboratory Medicine, v9 n3 p369-392 Sep 1989.

The Wilford Hall USAF Center HIV Scientific Study Group has continued our investigation into the Natural History of HIV disease in active duty USAF personnel and their dependents with intensive immunological evaluation and staging according to the Walter Reed staging classification. Significant progression over 12 months of observation appears to be approximately 10%. Studies to determine a marker of disease progression other than absolute CD4a lymphocyte counts are ongoing. Our large neurological natural history study has continued on all active duty HIV-seropositive individuals and they continue to receive full neurological evaluations as well as CSF analysis. Our data demonstrate that the CSF immune response is maximal in early-stage HIV disease and more blunted with respect to both absolute CSF lymphocyte numbers and B-cell immunologic response when CD4a counts drop below 400 cells/mm3. Keywords: HTLV III/HIV Natural history; HIV Disease progression; USAF Active duty military HIV, HIV Neurological disease; RAI; Prognostic markers of disease progression. (jes)

Infection with Human Immunodeficiency Virus type 1 (HIV-1), the etiologic agent of the acquired immune deficiency syndrome (AIDS), is increasing at an epidemic rate. The severity of immunologic impairment of infected individuals spans a broad range. It is not currently known whether this heterogeneity reflects distinct outcomes of infection or whether infection progress to a common endpoint at different rates. Developing closer knowledge of immunological events that precede the onset of frank AIDS, as well as the interplay between HIV, immunity and the hematopoietic elements that give rise to the attempts to develop better therapeutic approaches to AIDS. This proposal focuses on two primary areas. The first section, Interaction of HIV-1 and Bone Marrow, focuses on hematopoietic progenitor cells as possible reservoirs of virus. It is designed to explore the relationship between acquisition of lineage specific differentiated function and viral permissiveness, and examine the interaction of infected myeloid and lymphoid cells as they affect immune function and regulation of bone marrow growth. Our second research goal has been the Evaluation of Immunologic Changes Related to Progression of HIV Infection. This aspect of our research draws on the resources of two large prospective cohort studies of the natural history of HIV infection, one in gay/bisexual men (SHARE) and one in intravenous drug users (ALIVE).

It has previously been shown that infection of human CD4 cells with human immunodeficiency virus (HIV-1) results in the establishment of a chronic, non-cytopathic infection. We have recently found that cells infected with HIV-1 exhibit a specific impairment of cellular signalling. After polyclonal stimulation of the CD3/T cell receptor complex by anti-CD3 monoclonal antibody, the cells have a blunted or absent increase in the intracellular free calcium concentration within the first three minutes after simulation. In the present study we have investigated the mechanisms of the effect on cellular signalling by HIV-1. CD4 T cells were infected with HIV-1 and labeled with myoinositol. Inositol phosphate production was impaired after CD3 stimulation, suggesting that the effect of HIV-occurs at or before the activation of phosphoinositide specific phospholipase C. Recent studies have shown that the CD4 molecule is involved in cellular signalling with the T cell receptor as well as functioning as a receptor for MHC class II antigen and as the receptor for the HIV-1 virus. To further investigate the effects of HIV-1 on cellular signalling, the CEM leukemic T cell line was chronically infected with HIV-1, or a spontaneous mutant strain of HIV-1 that fails to cause modulation of the CD4 antigen. Calcium mobilization was impaired in cells infected with both strains of virus, indicating that impaired signalling is not simply the result of decreased surface expression of the CD4 receptor. Reprints. (kt), Published in Chemical Propulsion Information Agency Publication 517, v1 p165-176 Jun 1989.

Various epidemiologic patterns of HIV-2 and HIV-1 suggest both different population dynamics but also different origins. In HIV-2 prevalent areas, the virus demonstrates features of long-term endemicity. Incidence rates for HIV-2 are low as compared to that of HIV-1 and may reflect other in vitro characteristics; decreased infectivity and cytopathicity. Clinico-prospective studies have still failed to demonstrate AIDS or related symptoms in HIV-2 positive individuals followed both clinically and immunologically. RA 1; Human retroviruses; AIDS; HIV-1; HIV-2; SIV; West Africa. (kt)

Our long range goal is to understand the macromolecular interactions responsible for the integration of HIV DNA into human chromosomes. The primary goal of this project is to develop appropriate biochemical assays for the interaction of the HIV integration protein, IN, with a specific DNA target, the viral LTRs. The gene encoding IN has been subcloned from infectious viral DNA into appropriate cloning vectors and has been expressed in both E. coli and in insect cells. IN has been expressed as a pol fusion protein that is processed by HIV protease in vivo and as a single protein carrying an added methionine residue. The lack of any additional carboxy-terminal processing of IN has been demonstrated. Purification of the recombinant IN is in progress. Potential DNA substrates for IN have been constructed. These include a synthetic oligonucleotide substrate corresponding to the LTR end and a substrate containing the ligated junction of the two LTRs, obtained by polymerase chain amplification from HIV-infected cells. The latter provides both linear and circular DNA forms. During the construction of the circle junction clone, it was found that 50% of the circle junction sequences in infected cells are aberrant, containing deletions or insertions at the circle junction. The involvement of IN in the production of these forms will be investigated. Keywords: RA 1; Viral DNA; Viral endonuclease; Retrovirus; Lentivirus; Genome; Molecular virology.

The main objective of this study was to define the role of EBV in the progressive evolution of AIDS by means of a prospective evaluation of persons with HIV infections. Detailed EBV antibody responses and virologic studies to determine the EBV load in body fluids and EBV strains were performed serially. Current findings from this study indicate that reactivated type EBV infections are particularly prominent in the initial stages of the underlying HIV-1 infection. However, serologic response to EBV remains quite intense and abnormal through-out the early and late stages of the HIV-1 infection. The serologic findings are reflective of the abnormally elevated burden of transforming EBV present in oropharyngeal secretions and peripheral blood lymphocytes of patients with HIV-1 infection in all WR classes. Interestingly, the replicating form of the virus remains at highly elevated stages, i.e. Walter Reed classes 5 and 6. These high levels of EBV should be directly responsible for the emergence of EBV-related manifestations such as lymphoproliferative lesions and the increasing number of B cell lymphomas being reported in HIV-1 infected individuals. The tongue lesions, oral hairy leukoplakia, which may portend a poorer prognosis of the underlying HIV infection, represent a recently defined example of the EBV-related lesion containing an extremely high level of replicating EBV. The mechanism(s)responsible for the immunodysregulation of EBV in patients with HIV infections that permit the development of these EBV-related lesions is being investigated. (SDW)

Genetic and biologic studies of Human Immunodeficiency Virus Type 1 (HIV-1) aimed at developing an understanding of disease pathogenesis, viral evolution, and methods to treat and prevent infection have expanded to include study of the closely related human and simian immunodeficiency viruses. In our DoD funded work, we are pursuing the contract study aims by molecular analyses of HIV-1 and HIV-2, with focus on four primary aims i) nature and extend of genetic variation, ii) mechanism and rate of viral variation, iii) influence of host immune response on variation, and iv) effect of genetic variation on viral antigenicity, immunogenecity, and biology. In this annual report, we summarize results and conclusions obtained in the past year (year 02) in the areas of HIV- 1 variation in vivo and genetic and biologic analysis of HIV-2. In these studies, we have demonstrated for the first time that HIV-1 exists as a quasispecies, that genetic variation of HIV-1 develops in parallel with common viral forms persisting over time, and that changes in nucleotide and amino acid sequences accumulate in the envelope immunodominant loop region. In addition, recent clinical and seroepidemiological studies in West Africa indicate that HIV-2 is widespread and associated with immunodeficiency states of variable degree. In this study, a T-lymphotropic human retrovirus, HIV-2/ST, representing the first bone fide isolate of HIV-2 from Senegal was molecularly cloned and characterized in regard to its biologic and structural properties and its genetic relatedness to known primate retroviruses. Keywords: RA 1; AIDS; HTLV- III; Virology; HIX; Restriction maps; Genetic maps.

Genotypic variation among independent isolates of Human Immunodeficiency Virus Type 1 (HIV-1) is a widely recognized property of the virus. The molecular characteristics and biological consequences of HIV-1 variation in vivo, however, are only beginning to be understood and this information is essential for elucidation of disease pathogenesis and vaccine development. In the past year, we have examined the genesis of HIV-1 molecular variation in persistently infected individuals by preparing and analyzing recombinant HIV-1 lambda phage libraries from three virus isolates. Twenty-seven, 17, and 18 full-length HIV-1 clones were identified, mapped with 11 restriction endonucleases, and found to represent 17, 10, and 13 distinguishable but highly related viral genotypes, respectively. Recombinant viral clones from two HIV-1 isolates obtained from the same individual 16 months apart showed clear patterns of genotypic relatedness, yet progressive change. Similar changes in the HIV-1 genome did not occur in vitro during virus isolation and amplification. The results indicate that HIV-1 variation in vivo is rapid, that a remarkably large number of related but distinguishable genotypic variants evolve in parallel and coexist during chronic infection, and that isolates of HIV-1, unless molecularly or biologically cloned, generally consist of complex mixtures of genotypically-distinct viruses. Keywords: RA 1; AIDS; HTLV-III; Virology; HIV; Restriction maps; Gene mapping.

It has been shown that the major neutralizing determinant of HIV lies in the V3 segment of gp120, coded by a dominant, hypervariable region. A cocktail of V3 peptides will elicit, reproducibly, high anti-peptide and anti- HIV neutralizing activity for each isolate included in the cocktail. (KT)

Ribavirin (1-B-D-ribofuranosyl-1-1,2,4-triazole-3-carboxamide) or Virazole is a broad-spectrum antiviral agent whose molecular mode of action remains remarkably controversial. The drug was approved by the Food and Drug Administration in 1986 for aerosol use in infants with serious infections due to respiratory syncytial virus (RS). Ribavirin is and has been under clinical investigation against a variety of viral illness, including those due to influenza virus, Lassa fever, Korean hemorrhagic fever with renal syndrome (KHFS) and Human immunodeficiency virus (HIV). There has been a great deal of clinical interest in utilizing ribavirin for HIV infections. It has been reported to slow the development of AIDS in HIV infected patients (McCormick et al., 1984). We describe here the reported mechanisms of action of this newly licensed drug. (jg)

A seroepidemiologic survey was conducted among 773 male soldiers living in five urban locations in Sudan to study the prevalence of and risk factors for HIV-1 and hepatitis B transmission. Twenty-eight per cent of the study population were born and raised in southern Sudan, an area bordering Kenya, Zaire and Uganda, whilst 72% of the study subjects were from northern Sudan. Seventy-eight per cent of the study population had serologic evidence of past hepatitis B infection, and 13 soldiers were confirmed positive for HIV-1 antibody. All 13 HIV-positive soldiers had recently been deployed in southern Sudan. Multivariate analysis indicated an association between living in southern Sudan and both hepatitis B and HIV-1 infection. Additionally, sexual relations with prostitutes and medical injections for schistosomiasis, were independent predictors of hepatitis B markers in this military population. The findings of this study suggest that sexual promiscuity is a risk factor for hepatitis B transmission in Sudan. Keywords: HIV, Hepatitis B, Sexually transmitted disease, Reprints., Pub. in AIDS, V3 N11 P725-729 1989.

Several small animal models of HIV infection have been proposed. We have developed a means to support the replication of HIV-1 which can produce large populations of infected mice for therapy screening and host-virus interactions. Nude mice (3-4 wks old) were exposed to 600 R's of 137C's irradiation and inoculated with 1 x 107 HIV-1 infected CEM cells. The animals were followed daily for weight gain and tumor progression. Groups of 6 animals were exsanguinated at 8 intervals over a 9 week period and necropsies were performed. Plasma p24 antigen was detected at day 3 and rose over 9 weeks (2200 pg/ml). Where possible, plasma antigen was neutralized with human antisera to HIV-1. The infected mice did not exhibit any weight loss, but a highly significant difference was seen in tumor progression when compared to controls. Using immunohistochemistry, sheep raised polyclonal antibodies to viral p24 and gp 120 detected HIV proteins within tumor cells and mouse splenic macrophages. (JES)

A data collection research center has been established on Okinawa for the purpose of studying the risk of HTLV-I transmission to active duty personnel stationed there. Research activities have included an HTLV-I Seroprevalence Survey and a Prospective Serologic Study for HTLV-I seroconversion. A cross- sectional serologic survey of HTLV-I antibody was conducted among 5,255 active study U.S. Marines on permanent tour stationed in Okinawa, Japan to search for risk factors of seropositivity. Participants were primarily young caucasion males. Of the 28 screen positive samples, three were confirmed positive for HTLV-I by Western Blot analysis showing bands for core and envelope reactivity. All three seropositive cases have a history of prolonged sexual contact with Okinawan women and two of the three are married to infected Okinawan wives. Two gave a prior history for gonorrhea while all 3 were negative for syphilis (MHA- TP) and Hepatitis B. No other risk factors associated with HTLV-I seropositivity in the U.S. population are identified. These data suggest that female to male transmission of HTLV-I occurs in the absence of other cofactors, e.g., ulcerative genital lesions. (kt)

Monocytes and monocyte products have been shown to enhance markedly the growth of EBV-infected B cells; patients with AIDS have an increased frequency of EBV-infected B cells in their peripheral blood. The investigators have further shown that activated peripheral blood monocytes secretes beta 2/IL- 6 which promotes the growth of EBV-infected cells but, in general, IL-6 is not produced by EBV infected B cells. (aw)

This paper consists of a briefing or lecture outline on sexually transmitted diseases to be used by medical personnel as an instructional tool for a wide variety of audiences. It is intended to be used in whole or broken down to specific disease groups. It is to be accompanied by a set of 35 mm slides to be distributed separately through the Air Force Audiovisual Service (release date not established at this time). Human Immunodeficiency Virus (HIV) is not included since it is such a rapidly changing field. (kt)

Reverse transcriptase activity of the prototypic AIDS virus, HIV-1, was blocked in vitro by IgG derived from certain individuals infected with this retrovirus. A heterogeneous immune response for inhibition of enzyme function occurred. Loss of this inhibitor may be associated with development of clinical disease. Keywords: AIDS, Antibody, Clinical, HTLV-III, Infectious Diseases.

Acquired Immune Deficiency Syndrome is marked by a collapse in immune responses, particularly those mediated by thymus-derived (T) lymphocytes. Nevertheless, the presence of antibodies to the AIDS virus (HIV) indicates the presence of virus specific T cells. Over the last year we have defined cell tumors and populations which are much less susceptible to virus mediating killing. We are currently investigating how cells differ in the sensitivity to virus and how we can utilize this information therapeutically. Keywords: RA I; Lab animals; Rats; Volunteers; Vaccine development; Cellular immunity; Human immunodeficiency virus; Virology AIDS; Biotechnology; Monoclonal antibodies; Vaccines.

The main objective of this study was to define the role of EBV in the progressive evolution of AIDS by means of a prospective evaluation of persons with HIV infections. Detailed EBV antibody responses and virologic studies to determine the EBV load in body fluids and EBV strains were performed serially. The possible concurrent presence of HIV in EBV cell cultures established from body fluids from HIV infected persons also was examined. The HIV infected participants had an enhanced antibody response to a broad spectrum of EBV antigens. In addition, an increased amount of EBV was detected in oropharyngeal secretions as well as an increased proliferative ability of peripheral blood mononuclear cells compared to normal, healthy adults. The consequences of this highly increased burden of EBV in HIV patients are not well understood but could support the possibility that EBV may be a stimulus to produce tumors or other lymphoproliferative manifestations. The subgroup of patients with oral hairy leukoplakia (OHL) had an overall body burden of EBV, including a high density of replicating virus in the oral lesions, and more abnormal EBV antibody responses than HIV-infected personnel lacking OHL. This finding further strengthened the speculation that EBV is not well immunoregulated in HIV-infected patients and can lead to various lesions, some as lymphomas (reported by others) being quite deleterious. No correlation was noted between specific EBV genotypes and progression of the HIV infection, but the numbers tested (and the changes in disease progression) were small at this point in the study.

Molecular characterization of the SIV mac 251 clone that exhibits in vitro replication competence, but poor in vivo replication ability was initiated by complete nucleotide sequence determination. Defects in the vpr, nef and env genes were noted and will be the focus of future efforts to restore in vivo replication competence of this cloned virus. (js)

Reports of an increased proportion of AIDS cases occurring in small medium-sized cities suggest that the HIV epidemic may be spreading into locations that were previously characterized by their low HIV antibody prevalences. Studying the question of the geographic spread of the HIV infection epidemic (rather than the AIDS epidemic) has been difficult largely because most serial seroprevalence data have been gathered from cohorts of high risk individuals (e.g., homosexual, bisexual cohorts) in New York City, San Francisco, and other geographically circumscribed areas. The U.S. military applicant HIV screening data were used in the current report to examine rates and 24 month temporal trends in geographic areas characterized by their HIV endemicities. The data examined concern the seven most populous states and four hyperendemic metropolitan areas located with those states (New York City, Miami, Houston, and San Francisco). In the nonepidemic regions, seroprevalence rates increased among black and white applicants. Reprints., Published in the Journal of Acquired Immune Deficiency Syndromes, v2 p521-532, 1989.

A highly specific Enzyme-Linked Immunosorbent Essay system has been developed to detect circulating antibody in sera raised against the type- specific polar glycopeptidolipid antigens of Mycobacterium avium. These antigenic structures are unique to M. avium, and hence the purpose of the project was to exploit this knowledge to determine the prevalence of such antibodies in homosexual men at increased risk of Human Immunodeficiency Virus infection, and thus subsequent opportunistic infection with disseminated M. avium disease. Progress within the project to date has consisted of extraction of a large number of serotype-specific Glycopeptido Lipid antigens, and conformation of their purity using thin-layer chromatography and Gas Chromatography/Mass Spectrometry. The ELISA system was then initially tested for its specificity using a panel of monoclonal and polyclonal rabbit and mouse anti-GPL antibodies. RA 1, M. avium, In vivo, ELISA, Mycobacterium, Diagnostic serology.

The goal of this work is to develop novel, efficacious, injectable, gene-specific therapeutics for treatment of human immunodeficiency virus (HIV) infection. These products will be nuclease resistant, stereospecific antisense inhibitors of human immunodeficiency virus gene expression and activity. Antisense DNA inhibition has worked in this laboratory against several human and viral genes in cell culture. In this project, routes are being developed for the stereospecific synthesis and purification of all-S or all-R oligodeoxynucleoside methylphosphonates directed against specific HIV mRNAs, and against tat protein. Several dimers have been prepared by the pentavalent solution route, and encouraging results have been obtained for the trivalent solution route.

The study was undertaken in order to devise a quantitative assay of human immunodeficiency virus type 1 (HIV-1) load in patients' tissues. No methods are currently available which are both sensitive and specific for this purpose. Our methods utilizes blood mononuclear cell or tissue DNA. HIV-1 sequences are amplified by the primer chain amplification reaction (PCR) technique. The reaction products are detected and quantitated by polyacrylamide or agarose gel electrophoresis, ethidium bromide stain and densitometry. This method has proven successful using a single set of primers in detection of HIV-1 DNA sequences from 10 or 12 HIV-1 infected individuals, and 0 of 10 uninfected individuals. Methods of quantitation using standard curves with defined amounts of HIV-1 DNA sequences and internal controls have been developed. Preliminary experiments are reported applying this method to quantitation of HIV sequences in more than 50 patients. In addition, we have developed a sensitive and specific assay for HTLV-I and HTLV-II DNA sequences using the same methodology and we have successfully, applied it to the evaluation of blood samples from asymptomatic HTLV-I infected individuals and individuals with adult T cell leukemia-lymphoma.

The study was undertaken in order to devise a quantitative assay of human immunodeficiency virus type 1 (HIV-1) load in patients' tissues. No methods are currently available which are both sensitive and specific for this purpose. Our method utilizes blood mononuclear cell or tissue DNA. HIV-1 sequences are amplified by the primer chain amplification reaction (PCR) technique. Reaction products are detected and quantitated by polyacrylamide or agarose gel electrophoresis, ethidium bromide stain and densitometry. This method has proven successful using a single set or primers in detection of HIV-1 DNA sequences from 10 of 12 HIV-1 infected individuals, and 0 out of 10 uninfected individuals. Methods of quantitation using standard curves with defined amounts of HIV-1 DNA sequences and internal controls have been developed. We have developed a sensitive and specific assay from HTLV-I and HTLV-II DNA sequences using the same methodology and successfully applied it to the evaluation of blood samples from asymptomatic HTLV-I infected individuals and individuals with adult T cell leukemia-lymphoma.

We identified Campylobacter jejuni infections in four patients infected with the human immunodeficiency virus (HIV); three had persistent and severe C. jejuni infections. Multiple isolates obtained from each patient had the same biochemical and serotypic characteristics, indicating recurrent infection rather than reinfection with unrelated strains. Serum antibody responses to C. jejuni group antigens by enzyme-linked immunosorbent assay were markedly impaired in the three patients with persistent infection compared with forty-two immunocompetent C. jejuni-infected controls and with the HIV-infected patient who readily cleared the organism. One patient was bacteremic; his blood isolate was killed by normal serum but was resistant to his own serum, whereas a simultaneous stool isolate of a different serotype was sensitive. Failure of two patients to eradicate the organism and long-term administration of erythromycin therapy led to the in-vivo development of resistance to this antibiotic, which is most frequently used to treat C. jejuni infections

This Worldwide Report contains articles on Epidemiology.

Partial Contents: Meningitis, Governments, AIDS cases, Infectious Diseases, Dengue, Fever, Malaria, Parasites, Bacterial Diseases, Skin Infections, Health Department, Immunology, Leprosy Control, HIV Positive Cases, Doctors.

Monoclonal murine IgG antibodies against Gp120 from HIV-1 were found to induce significant enhancement of HIV-1 replication in vitro when used at low antibody concentrations. This enhancement was dependent on the presence of FcR:s for IgG and was completely blocked by anti-CD4 monoclonal antibodies. HIV-1 seropositive individuals at a low frequency do produce antibodies reactive with Gp12O and 'mimicking' CD4 molecules as evidenced by their reactivity with certain CD4 monoclonal antibodies. It was, however, not possible to show that such 'mimicking' antibodies were especially efficient in neutralizing, nor was presence of such antibodies linked to a particular clinical progression behaviour. Presence of antibodies to peptides covering the respective cysteins in the V3 loop of a particular HIV-1 isolate were found using two Italian cohorts to be positively linked to a reduced rate of transmission of virus from mother to child.

Gp120 binding to CD4 requires beta-glycanase sensitive carbohydrate chains to retain binding ability. A 28Kd fragment of Gp120 has been identified with complete retention of CD4 binding capacity. Human monocytes can be readily infected with HIV. In the absence of anti-HIV antibodies, phagocytic or non-phagocytic monocytes are equally sensitive. Anti-HIV antibodies at certain high dilutions may enhance HIV proliferation in human monocytes although exact conditions causing such enhancement are not yet defined. Certain human HIV-seropositive individuals produce high titered antibodies which display molecular mimicry with CD4 and bind to Gp120. Such antibodies may tentatively be linked to good prognosis. Keywords: Human immunodeficiency virus, Immunosuppression, Immunity.

The molecular basis of infectivity, cytopathogenicity and genomic activation of Human Immunodeficiency Virus Type 1(HIV-1) was investigated by generating deletion mutations in sor, 3'orf, 5' region, and LTR. These studies show that the sor gene is crucial for the generation of infectious virus. Analysis of 3'orf indicate that deletions in the amino terminus (which overlaps the carboxy terminus of gp41) result in significant reduction in viral propagation. Studies with the LTR sequency have delineated an enhancer activity, an sp-1 bending site, and a tat response region (TAR). Genomic clones containing the integrated provirus of Simian T-Cell Lymphotorpic Virus Type III(African Green Monkey) (STLV-II(AGM)) and HIV-2(NIH-Z) have been isolated. Their nucleic acid sequence has been determined and subjected to computer analysis. A Comparison of the nucleotide sequences of these two new viral isolates with HIV-1 indicates that these new retroviruses are structurally similar to HIV-1 and belong to the same class of viruses as HIV-1. STLV-III and HIV-2(NIH-Z) exhibit a greater homology among themselves than with HIV-1. A study of biologically active forms of these viruses will aid in understanding why these new viruses are non-pathogenic. Keywords: Vaccines, Acquired immune deficiency syndrome, Virus diseases, Immunosuppression, Deoxyribonucleic acids.

The purpose of the research program is to define immune responses of humans to Human Immunodeficiency Virus (HIV) infection and the cause of the Acquired Immune Deficiency Syndrome (AIDS). Immunodeficiency caused by HIV infections may be due to immune mediated lysis (by antibody and/or HIV specific cytotoxic T lymphocytes (CTL) of infected macrophages and T4 lymphocytes. The definitions of these immune responses to HIV virus are needed for rational approaches for therapy and prevention. Since the project began in October, 1986, we have developed an integrated program of research projects to develop experimental systems required for defining the immune responses of humans to HIV.