AIDS-like Syndrome Research Articles

Incidence, trends, and significance of putative koala retrovirus-associated diseases in monitored wild koala populations in southeast Queensland. In Proceedings of the Second Koala Retrovirus Workshop, ed. D. E. Alquezar-Planas, D. P. Higgins, C. L. Singleton, and A. D. Greenwood

Research indicates that northern koalas (Phascolarctos cinereus) are ubiquitously infected with koala retrovirus (KoRV). There is increasing evidence linking KoRV with neoplasia and a range of disorders associated with immunodeficiency, conditions observed at high rates in captive colonies, and sick koalas presenting to wildlife hospitals. However, less is known about the occurrence of these putative KoRV-associated diseases in wild populations. We analysed health data collected at the veterinary examinations of 691 koalas inhabiting three monitored wild koala populations in southeast Queensland between 2013 and 2020. At initial presentation, neoplasia and AIDS-like syndrome were detected at a prevalence of 1.16% (8/691; 95% CI 0.5–2.19%). Longitudinal data from koalas recruited into the monitoring programmes and receiving one or more subsequent examination revealed an incidence rate of 3.5 cases/100 koalas/year (95% CI 2.35–4.9). These findings indicate that a relatively small proportion of the populations studied were affected by these putative KoRV-associated diseases. However, the impact on individuals was severe, with high associated mortality in the diseased cohort. Furthermore, northern koala populations endure multiple threats, suffering severe declines in recent decades. We propose that the significance of putative KoRV-associated diseases on these populations should be considered within this context and that further research into the interactions between KoRV and other drivers of decline is warranted.

Anti-Interferon Autoantibodies in Adult-Onset Immunodeficiency Syndrome and Severe COVID-19 Infection

Adult-onset immunodeficiency syndrome due to anti-interferon (IFN)-γ autoantibodies has attracted much attention in recent years. It usually occurs in previously healthy people and usually presents as chronic, recurrent, and hard-to-control infections that can be effectively treated with aggressive antibiotic therapy. Adult-onset immunodeficiency syndrome is also referred to as AIDS-like syndrome. Anti-type I IFN (IFN-I) autoantibodies have been reported to play a significant role in the pathogenesis of coronavirus disease 2019 (COVID-19) and preexisting anti-IFN-I autoantibodies are associated with an increased risk of severe COVID-19. This review summarizes the effects of anti-IFN autoantibodies on the susceptibility and severity of various infectious diseases, including SARS-CoV-2 infection. In addition, we discuss the role of anti-IFN autoantibodies in the pathogenesis of autoimmune diseases that are characterized by recurrent infections.

Antibodies drive an aids-like syndrome

Researchers identify a new AIDS-like disease caused by IFNγ-specific autoantibodies.

Anti-Inflammatory Therapy for Feline Immunodeficiency Virus Infection and Associated AIDS-Like Syndrome

Feline immunodeficiency virus (FIV) is a lentivirus that can infect several feline species, among them the domestic cat. Related lentiviruses are prevalent in non-domestic felids (Olmsted et al., 1992). The isolation of FIV from cats who while having an immunodeficiency-like illness were seronegative for Feline leukemia virus (FeLV), was first described in 1987 (Pedersen et al., 1987). FIV is classified into five phylogenetic subtypes, A through E, according to the nucleotide sequence diversity in the env gene that encodes for the viral envelop proteins. Subtypes A and B are most prevalent worldwide (Samman et al., 2011). The seroprevalence differs between regions, with 1–14% in clinically asymptomatic domestic cats and up to 44% in sick cats (Hosie et al., 2009). Feline immunodeficiency virus transmission occurs naturally mainly through biting, but vertical transmission between mother and kittens is also possible (Yamamoto et al., 1989). Transmission occurs more easily when an uninfected cat is exposed to infected cells, although lower levels of the virus are also present in colostrum, saliva, plasma, and seminal fluid (Yamamoto et al., 2007). After acute infection FIV can cause a AIDS-like syndrome in domestic cats, with many similarities to HIV-induced AIDS in man (Elder et al., 2010). Progression of the chronic lentivirus infection is associated with a decline in CD4+ T lymphocytes and CD4+:CD8+ ratio during a asymptomatic phase. During this period plasma virus load remains stable (Hosie et al., 2009). When the CD4+ T lymphocyte count falls below a certain number immune dysfunction will become apparent, accompanied by secondary and opportunistic infections (Willett et al., 1997). In addition to the ability to infect CD4+ T lymphocytes, FIV also infects several other immune cells, including monocytes/macrophages, B cells, CD4+CD25+ T cells, and CD8+ T cells (Yamamoto et al., 2007). Currently practiced therapy focuses on immune stimulation, vaccination, and treatment of secondary diseases. Immune stimulation has been suggested in the form of GM-CSF, IFN-alpha, and IFN-tau among others (Arai et al., 2000; Pedretti et al., 2006; Chon and Bixler, 2010). These therapies are based on the notion that the CD4+ T lymphocyte depletion in feline AIDS is the direct consequence of viral killing by FIV (the “viral killing hypothesis”). In this theory high turnover of T lymphocytes and eventually exhaustion is a response to viral destruction of CD4+ T lymphocytes. It has also been suggested however, that activation-induced CD4+ T lymphocyte death may be a major factor in progression to AIDS in humans (Groux et al., 1992; Hazenberg et al., 2003), which corresponds with the absence of CD4+ T lymphocyte decline in naturally Simian immunodeficiency virus (SIV) infected Sooty Mangabeys (Silvestri et al., 2003). These primates show a high viral load, but limited SIV CD4+ T lymphocyte cytopathicity. Therefore chronic (hyper-)activation of the immune system may also play a significant role in FIV pathogenesis (Figure ​(Figure1).1). This hyper-activation is seen in both CD4+ and CD8+ T lymphocyte populations, with a rise in B7+CTLA4+ phenotype, and increase in B lymphocyte polyclonal responses (Tompkins and Tompkins, 2008). The B7+CTLA4+ T lymphocytes cause an induction of anergy and apoptosis through T–T lymphocyte interactions, which leads to CD4+ T lymphocyte depletion. Figure 1 Chronic antigenemia induces immune hyper-activation that leads to immune suppression. This process may be inhibited by anti-inflammatory or immunosuppressive drugs that reduce T-cell activation. Partly the depletion of CD4+ T lymphocytes may also be due to the activation of CD4+CD25+ T regulatory (Treg) cells in FIV-infected cats. Previous studies suggested that a proper immune response is lost during the acute phase FIV infection (Mexas et al., 2008). It's possible that CD4+CD25+ T regulatory lymphocytes induce anergy in CD4+ and CD8+ T cells (Vahlenkamp et al., 2004). This knowing, it could be meaningful investigating which mechanisms cause the activation of CD4+CD25+ Treg cells and if it can be suppressed effectively during the acute phase of FIV infections, without losing an effective immune response. CD4+ and CD8+ T-cells functioning may improve when CD4+CD25+ Treg cells are suppressed and slow progression to AIDS. In light of this evidence it is important to explore the effectiveness of immunosuppressive or anti-inflammatory treatment in the prevention of progression to AIDS in FIV-infected cats. Suggested pharmaceuticals for this type of treatment for HIV are cyclosporin A and corticosteroids (Groux et al., 1992; Lawn et al., 2001). It should however be noted that although this type of treatment may diminish the detrimental effect of immune hyper-activation, antiretroviral drugs, that for example inhibit FIV enzymes (Savarino et al., 2007), should be used or developed to alleviate the potential effects of immunosuppression on viral replication.

FELINE IMMUNODEFICIENCY VIRUS AND ITS RECEPTORS

Feline immunodeficiency virus (FIV) is a lentivirus associated with an AIDS-like syndrome in the domestic cat. The hallmark of the infection is a gradual depletion of CD4+helper T lymphocytes. The FIV enter cells by sequential interaction between its envelope glycoprotein (ENV) and the primary receptors, CD 134, and subsequently with the co-receptor the chemokine recepotrs CXCR4. The expression of those receptors is restricted to activated cells. The FIV possesses a broad tropism for CD4+lymphocytes, CD8+lymphocytes, B lymphocytes and monocyte-derived macrophages. CD4+ cell has the greatest provirus burden during the acute phase of infection but during the chronic phase, asymptomatic stage, B cells bears the major FIV provirus. This change could be the result of the different way that the ENV interacts with its receptors. This review is a brief overview of the interaction between FIV and its receptors. The molecular mechanisms of this relation and the viral cell tropism with disease progression not only did are important to development of vaccine approaches and therapeutic interventions but also to the understanding of pathogenesis of lentiviruses. DOI: http://dx.doi.org/10.17525/vrr.v15i1.39

Design and synthesis of membrane fusion inhibitors against the feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a pathogenic virus that causes an AIDS-like syndrome in the domestic cats. For viral entry and infection, fusion between the virus and the cell membrane is the critical process and this process is mediated by an envelope glycoprotein gp40. We have identified fusion inhibitory peptides from the heptad repeat-2 (HR2) of gp40. Remodeling of the original sequences using α-helix-inducible motifs revealed the interactive residues of gp40. Comparative analysis of HR2 peptides derived from four FIV strains demonstrated that the interactive surface of the Shizuoka strain-derived HR2 peptides provides the highest affinity of all the FIV strains examined.

The drug monosodium luminol (GVT ®) preserves thymic epithelial cell cytoarchitecture and allows thymocyte survival in mice infected with the T cell-tropic, cytopathic retrovirus ts1

A mutant of MoMuLV, called ts1, causes an AIDS-like syndrome in susceptible strains of mice. In mice infected at birth, thymic atrophy, CD4+ T cell loss, body wasting, and death occur by ∼30–40 days postinfection (dpi). We have shown previously that the death of ts1-infected cells is not caused by viral replication per se, but by oxidative stress and apoptosis following their accumulation the ts1 viral envelope precursor protein, gPr80 env. In infected mice treated with the antioxidant monosodium α-luminol (GVT ®), T cell loss and thymic atrophy are delayed for many weeks, and body wasting and death do not occur until long after infected, untreated control mice have died. We show here that GVT treatment of ts1-infected mice maintains the thymic epithelial cell (TEC) cytoarchitecture and cytokeratin gradients required for thymocyte differentiation. It also suppresses thymocyte reactive oxygen species (ROS) levels, upregulates and stabilizes levels of the antioxidant-regulating transcription factor Nrf2, and prevents accumulation of gPr80 env in thymocytes. We conclude that GVT treatment can make ts1 a non-cytopathic virus for thymocytes, although it cannot prevent thymocyte infection. Since oxidative stress also contributes to the loss of T cells in HIV-AIDS, the antioxidant effects of GVT may make it a useful therapeutic adjunct to HAART treatment.

Low-dose interferon-α treatment for feline immunodeficiency virus infection

Feline immunodeficiency virus sustains an AIDS-like syndrome in cats, which is considered a relevant model for human AIDS. Under precise enrolment requirements, 30 naturally infected cats showing overt disease were included in a trial of low-dose, oral human interferon-α treatment. Twenty-four of them received 10 IU/Kg of human interferon-α and 6 placebo only on a daily basis under veterinary supervision. The low-dose human interferon-α treatment significantly prolonged the survival of virus-infected cats ( p < 0.01) and brought to a rapid improvement of disease conditions in the infected hosts. Amelioration of clinical conditions was neither correlated with plasma viremia, nor with proviral load in leukocytes. A good survival of CD4+ T cells and a slow increase of CD8+ T cells were also observed in human interferon-α-treated cats. Interestingly, the improvement of the total leukocyte counts showed a much stronger correlation with the recovery from serious opportunistic infections. As shown in other models of low-dose interferon-α treatment, there was a rapid regression of overt immunopathological conditions in virus-infected cats. This hints at a major role of interferon-α in the control circuits of inflammatory cytokines, which was probably the very foundation of the improved clinical score and survival despite the unabated persistence of virus and virus-infected cells.

LP-BM5 infection impairs acquisition, but not performance, of active avoidance responding in C57B1/6 mice.

LP-BM5 murine leukemia virus infection causes an AIDS-like syndrome--murine acquired immunodeficiency syndrome--in C57B1/6 mice and impairs spatial learning in the Morris water maze without gross motor impairment. We used a shuttle shock-avoidance procedure to examine the effects of LP-BM5 infection on learning and retention of avoidance behavior. Thirty mice were inoculated with LP-BM5; 30 received vehicle (DMEM) injections. Fifteen LP-BM5 and 15 DMEM mice were trained in avoidance 7 wk after inoculation; retention of the avoidance response was tested 4 wk later. The remaining mice were trained 11 wk after inoculation. In animals trained 7 wk after inoculation, the groups performed similarly, with a marginally significant tendency for LP-BM5-infected animals to make more avoidance responses. This group difference was significant when animals were retested at 11 wk. However, LP-BM5 animals trained 11 wk after inoculation made significantly fewer avoidance responses than controls trained at the same time. We conclude that in later stages of disease, LP-BM5 impairs response acquisition, but not performance, in the active avoidance procedure. Results extend the use of the LP-BM5-infected mouse as a model of AIDS dementia complex.

Molecular Cloning of the Human Immunodeficiency Virus Subtype 2 Strain HIV-2UC2

An infectious molecular clone was derived from the HIV-2UC2isolate that previously was found to persistently infect and induce an AIDS-like disease syndrome in baboons. The molecularly cloned virus (HIV-2UC2mc) showedin vitroproperties similar to those of the parental isolate with regard to T-cell tropism, cytopathicity, and the ability to infect primary baboon PBMC. Nevertheless, when inoculated into two baboons, the cloned virus showed a limited ability to replicate in these animals. DNA sequence analysis revealed a defectivevprgene in the UC2mc as well as in the pathogenic parental UC2 strain. Thus, thevprgene is not required for the induction of disease in baboons. The attenuated infectious molecular clone of UC2 should be useful for future studies designed to map the genetic determinants of HIV-2 pathogenesis in the baboon model and to evaluate vaccine strategies.

Molecular and biological analyses of quasispecies during evolution of a virulent simian immunodeficiency virus, SIVsmmPBj14.

A prototypic simian immunodeficiency virus (SIVsmm9), isolated from a naturally infected sooty mangabey (Cercocebus atys), was passaged in vivo in a pig-tailed macaque (Macaca nemestrina) having the identifier PBj. When PBj died of a typical AIDS-like syndrome 14 months after infection, the virus isolated from its tissues was subsequently shown to differ from SIVsmm9 genetically and biologically. Most notably, this isolate, SIVsmmPBj14 (SIV-PBj14), is the most virulent primate lentivirus known: it induces acute disease and death within 6 to 10 days after intravenous inoculation into pig-tailed macaques. Between the time of infection with SIVsmm9 and isolation of SIV-PBj14, isolates were obtained periodically from peripheral blood mononuclear cells of PBj. To establish the temporal relationship between evolution of new biologic properties and fixation of specific mutations in the virus population, these sequential SIV-PBj isolates were characterized for unique properties of SIV-PBj14 that appeared to correlate with acute lethal disease. These properties included the ability to replicate in quiescent macaque peripheral blood mononuclear cells, to activate and induce proliferation of CD4+ and CD8+ cells, and to exhibit cytopathicity for mangabey CD4+ lymphocytes. Consistent with earlier studies, a major change in biologic properties occurred between 6 (SIV-PBj6) and 10 (SIV-PBj10) months, with the SIV-PBj8 quasispecies exhibiting properties of both earlier and later isolates. Multiple biologic clones derived from the 6-, 8-, and 10-month isolates also exhibited diverse phenotypes. For example, one SIV-PBj10 biologic clone resembled SIVsmm9 phenotypically, whereas three other biologic clones resembled SIV-PBj14. To evaluate genetic changes, proviral DNA of the biologic clones generated from SIV-PBj6, -PBj8, and -PBj10 was amplified by PCR in the U3 enhancer portion of the long terminal repeats (LTR) and the V1 region of env, where the greatest nucleotide diversity between SIVsmm9 and SIV-PBj14 resided. Nucleotide sequence data indicated that all biologically cloned viruses are distinct and that insertions/duplications of 3 to 27 nucleotides (in multiples of three) had accumulated stepwise in the env V1 region, beginning with SIV-PBj8. In addition, one of four SIV-PBj8 biologic clones had a 22-bp duplication in the LTR which is characteristic of SIV-PBj14. When virus mixtures containing different proportions of two SIV-PBj10 biologic clones with opposite phenotypes were tested, the SIV-PBj14 phenotype was clearly dominant, since mixtures with as few as 10% of the viruses being SIV-PBj14-like exhibited all the properties of the lethal isolate.(ABSTRACT TRUNCATED AT 400 WORDS)

Induction of AIDS by simian immunodeficiency virus from an African green monkey: species-specific variation in pathogenicity correlates with the extent of in vivo replication

Previous studies suggested that simian immunodeficiency viruses isolated from African green monkeys (SIVagm) are relatively nonpathogenic. The report describes the isolation and biologic and molecular characterization of a pathogenic SIVagm strain derived from a naturally infected African green monkey. This virus induced an AIDS-like syndrome characterized by early viremia, frequent thrombocytopenia, severe lymphoid depletion, opportunistic infections, meningoencephalitis, and death of five of eight macaques within 1 year after infection. An infectious clone derived from this isolate reproduced the immunodeficiency disease in pig-tailed (PT) macaques, providing definitive proof of the etiology of this syndrome. Although the virus was highly pathogenic in PT macaques, no disease was observed in experimentally infected rhesus macaques and African green monkeys despite reproducible infection of the last two species. Whereas infection of PT macaques was associated with a high viral load in plasma, peripheral blood mononuclear cells, and tissues, low-level viremia and infrequent expression in lymph nodes of rhesus macaques and African green monkeys suggest that differences in pathogenicity are associated with the extent of in vivo replication. The availability of a pathogenic molecular clone will provide a useful model for the study of viral and host factors that influence pathogenicity.

Development Of Clinical Disease In Cats Experimentally Infected With Feline Immunodeficiency Virus

Cats naturally infected with feline immunodeficiency virus (FIV) develop an AIDS-like syndrome whereas experimentally infected cats do not. To investigate the role of cofactors in the development of this disease in cats, 7 specific pathogen-free (SPF) and 12 random-source (RS) cats were infected with FIV. Over 4 years, infected cats developed similar phenotypic and functional immune abnormalities characterized by early and chronic inversion of CD4+:CD8+ cell ratios and significantly decreased mitogen responses compared with controls. Beginning 18-24 months after infection, 10 RS cats developed chronic clinical disease typical of feline AIDS, including stomatitis and recurrent upper respiratory disease; 4 SPF cats also developed chronic clinical disease, 2 with neurologic disease and 2 with B cell lymphomas. Thus, immunologic background is important in the type of disease that develops in cats infected with FIV, and FIV represents a promising animal model for studying the immunopathogenesis of AIDS in humans.

Growth Failure and AIDS-like Cachexia Syndrome in HIV-1 Transgenic Mice

The mechanisms which predispose to growth failure in infants and children infected with immunodeficiency virus type-1 (HIV-1) are not fully understood. The contributions of viral replication and CD4+ T cell depletion to growth failure in an HIV-1 transgenic mouse model were investigated. Mice homozygous for the transgene, a gag-pol deletion mutant of the HIV-1 provirus pNL4-3, exhibited marked cachexia, growth retardation, lymphoproliferation with a reduction in the percentage of CD4+ T cells but an increase in the absolute number of splenic CD4+ and CD8+ T cells, thymic hypoplasia, and early death. Despite the absence of T cells, athymic nude mice, homozygous for the HIV transgene, displayed comparable growth failure. The results indicate that AIDS-like cachexia may be produced by expression of viral envelope or accessory genes, need not be accompanied by absolute depletion of CD4+ T cells, and may occur independent of T cell function.

In vitro susceptibility of Macaca nemestrina to human herpesvirus 6: a potential animal model of coinfection with primate immunodeficiency viruses.

Human herpesvirus 6 (HHV-6), a lymphotropic herpesvirus, has been suggested as a potential cofactor in the acquired immunodeficiency syndrome (AIDS). Previous studies indicate that HHV-6 has a restricted range of susceptible species. In this study, we tested the in vitro susceptibility to HHV-6 of Macaca nemestrina (pig-tailed macaque), a species that has been found to be infectable by human immunodeficiency virus type I in vivo and that develops an AIDS-like syndrome following simian immunodeficiency virus (SIV) infection. Two different HHV-6 isolates (HHV-6GS and HHV-6BA), belonging to the two major HHV-6 variants (A and B, respectively), were employed. Both viruses induced a productive and cytopathic infection in phytohemagglutinin-stimulated peripheral blood T lymphocytes from M. nemestrina. In contrast, only HHV-6BA (variant B) was able to replicate in lymphocytes from Macaca mulatta (rhesus macaque). Moreover, HHV-6GS and SIVsmE660 productively coinfected individual M. nemestrina lymphocytes, resulting in increased levels of SIV replication. Genetic sequences of HHV-6 were not amplified by polymerase chain reaction from peripheral blood mononuclear cells of several adult M. nemestrina, suggesting that these animals, unlike humans, are not commonly infected by HHV-6, or a related virus. Thus, M. nemestrina may represent an optimal animal model system to investigate the in vivo interactions between HHV-6 and the primate immunodeficiency viruses.

Isolation of a type D retrovirus from B-cell lymphomas of a patient with AIDS

An atypical syncytial variant of a high-grade Burkitt's-type B-cell lymphoma from a patient with AIDS who was seropositive for human immunodeficiency virus type 1 was studied. A productive type D retrovirus infection was identified in early-passage cell lines derived from two lymphomas from this patient. Nucleotide and amino acid sequence analysis as well as immunologic reactivity indicated that the isolated virus was highly related to Mason-Pfizer monkey virus (MPMV). MPMV is an immunosuppressive type D retrovirus that causes an AIDS-like syndrome in rhesus macaques. Amplification of DNA from the patient's diagnostic bone marrow biopsy specimen by polymerase chain reaction generated the appropriate MPMV-specific fragments and indicated that the patient was infected with the MPMV-like retrovirus. In addition, the patient's serum contained antibodies which recognized type D viral env proteins (gp70 and gp20) and gag proteins (p27 and p14). Although there have been reports of human cell lines infected with type D retroviruses and of type D-reactive human sera, this is the first evidence of a type D retrovirus infection in a human confirmed by virus isolation, serum reactivity, and viral DNA identification in tumor tissue.

Factors Associated with AIDS and AIDS-Like Syndrome among Homosexual and Bisexual Men in Minas Gerais, Brazil

A case-control study to determine factors associated with AIDS and AIDS-like syndrome among homosexual/bisexual men was conducted in the State of Minas Gerais (Brazil). Eighty-three per cent (45 patients) of all AIDS/AIDS-like syndrome cases in homosexual/bisexual men reported in Minas Gerais between February, 1986 and June, 1987 were compared to 133 seronegative controls seen at the same clinic. Blood samples were tested by ELISA and confirmed by Western blot. Sex with men from the USA, sex with someone who developed AIDS, number of male partners (greater than or equal to 100 lifetime), age (greater than or equal to 30 years old) and ethnicity (white) were independently associated with AIDS/AIDS-like syndrome (Odds Ratios = 5.5, 4.3, 3.9, 3.5 and 2.7, respectively). Thirty-nine per cent of cases and 44% of controls reported bisexual activity during the previous two years. From these, a high proportion reported anal intercourse with women in the same period (53% of bisexual cases and 33% of bisexual controls). Bisexual men had more male partners than female partners in the previous two years (median male partners = 20 for cases and five for controls; median female partners = three for both cases and controls). This explains in part why the epidemic has increased more rapidly among men then among women in Minas Gerais, despite the large proportion of bisexuals with the disease.

Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques

The CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV-1) and a soluble truncated form of CD4 produced by recombinant DNA technology is a potent inhibitor of HIV-1 replication and HIV-1-induced cell fusion in vitro. Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVMAC), a virus closely related to HIV-1, develop an AIDS-like syndrome, and so provide an important model for the evaluation of potential AIDS therapies. We have assessed the therapeutic effect of recombinant soluble CD4 in SIVMAC-infected rhesus monkeys. Virus was readily isolated from peripheral blood lymphocytes and bone marrow cells of these animals before starting treatment with soluble CD4, but became difficult to isolate soon after treatment had begun. Moreover the diminished growth of both granulocyte-macrophage and erythrocyte progenitor colonies from the bone marrow of these monkeys rose to normal levels during treatment. These findings indicate that soluble CD4 could prove valuable in the treatment of AIDS.

T-CELL DEFICIENCY IN AN AFRICAN FAMILY

We report the case of a 19-month old African boy born from parents with clinical and immunological features suggesting prodromal acquired immunodeficiency syndrome (AIDS). He showed early failure to thrive, generalized lymphadenopathy, bilateral parotitis. Later he developped persistent interstitial pneumonia, persistent oral thrush and mild hepatosplenomegaly. Immunological studies showed hyper IgG level (3.2 g/dl), reversed T-helper/T-suppressor (T4/T8) ratio (19/68) and T-cell defect (cutaneous anergy for different antigens, depressed in vitro response for concanavalin, phytohaemagglutinin and Pokeweed mitogens). Open lung biopsy showed interstitial nodular lymphocytic infiltrates on optic microscopy and cytoplasmic particles on electron microscopy which are of uncertain origin. Recently the two older brothers were investigated. The oldest (6 years) showed chronic parotitis, hyper IgG level (4.7 g/dl), reversed T4/T8 ratio (18/49) and depressed in vitro response to mitogens. The second (5 years) showed slight parotitis, reversed T4/T8 ratio (29/32) and depressed in vitro response to mitogens. Both had normal chest X-rays The clinical and immunological presentation of the three children resemble that of infants with AIDS-like syndrome described by others in the USA. We suggest specific modes of transmission could be involved in familial acquiring of AIDS (transplacental-route, breast feeding, or other routine close-contact).