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Biomedical subjects

P Putkonen

Publications and source records attributed to P Putkonen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Simian immunodeficiency virus (SIVsm) isolation from blood and brain of experimentally infected macaques.

The possibility of using simian immunodeficiency virus (SIV)-infected macaques to study pathogenic events linked to HIV infection of the brain prompted us to investigate some of the virological features in SIV-infected macaques. Nine cynomolgus macaques were inoculated with SIVsm and killed at different times. We successfully isolated virus from the blood of all the animals and from the brains of eight. These results point to the early and regular spread of this lentivirus to the brain. Neutralizing activity was studied in the serum and cerebrospinal fluid specimens obtained from these macaques against a selected group of isolates. Cerebrospinal fluid did not show any neutralizing activity. Our findings integrate the observations from HIV-1 infection in man and indicate that SIV infection of macaques is a useful model for studying pathogenic events of brain infection.

Animals↗
PubMed1991

A capture enzyme immunoassay for detection of HIV-2/SIV antigen.

An antigen capture enzyme immunoassay was developed for the demonstration of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV). The assay (HIV-2 CE) has a sensitivity of approximately 250 pg/ml of HIV-2/SIV antigen. The HIV-2 CE was 4-16 times more sensitive than the Abbott HIV-1 antigen assay for detection of HIV-2/SIV antigen in cell culture supernatant. The sensitivity for detection of HIV-2/SIV antigen in serum or plasma was 98.5% in the HIV-2 CE and 95.5% in the Abbott HIV-1 antigen assay. The specificity of the HIV-2 CE was 99.2% (one false positive among 119 negative sera) whereas the Abbott assay was 100% specific. The HIV-2 CE detected antigen in supernatants from cultures of peripheral blood mononuclear cells of macaque monkeys infected with HIV-2 or SIV about 1 week before a reverse transcriptase (RT) microassay was positive and remained positive for at least 1 week after the RT assay had become negative. Three cultures from persistently infected monkeys were positive only in the HIV-2 CE, reflecting a higher sensitivity compared to the RT microassay. Thus, the HIV-2 CE was more sensitive than the Abbott HIV-1 antigen assay for detection of HIV-2/SIV antigen in culture supernatants as well as in serum/plasma. Furthermore, the HIV-2 CE showed a higher sensitivity than the RT microassay for detection of HIV-2/SIV in cell culture supernatants.

Animals↗
PubMed1990

Infection of cynomolgus monkeys with HIV-2 protects against pathogenic consequences of a subsequent simian immunodeficiency virus infection.

Simian immunodeficiency virus (SIV) infection in cynomolgus macaques leads to severe immunodeficiency with a fatal outcome. In contrast, HIV-2 infects these primates without apparently causing any immunological abnormalities. In this study three cynomolgus monkeys were experimentally infected with HIV-2 strain SBL-K135 and 168 days later challenged with 10-100 animal infectious doses of the closely related SIV strain SM to study protective immunity. At the time of SIV challenge the HIV-2-infected monkeys had neutralizing antibodies against HIV-2, but virus could no longer be recovered from their peripheral blood mononuclear cells (PBMCs) and no clinical symptoms or decrease in CD4+ lymphocytes were observed. Follow-up for 9 months after challenge with SIV showed that the HIV-2-infected monkeys were protected against SIV-induced immunodeficiency (no decrease of CD4+ lymphocytes) and lymphadenopathy. However, they were not resistant to SIV infection since virus could be recovered from their PBMCs and they developed anamnestic antibody responses. Four naive control monkeys which were inoculated with the same dose of SIV became persistently infected and developed a decrease of the absolute numbers of CD4+ cells and showed a marked lymphadenopathy. Two out of four control animals died 58-265 days postinfection with an immunosuppressive disease. Immunohistochemical examination showed abundant viral antigen in lymph-node biopsies from the SIV-infected control monkeys but absence of SIV or HIV-2 antigens in the biopsies from the three HIV-2-preinfected and SIV-superinfected monkeys. The present study demonstrates possibilities for induction of immunity against immunodeficiency induced by a primate lentivirus, a concept with application also to HIV infection and AIDS in man.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Malignant lymphomas in cynomolgus monkeys infected with simian immunodeficiency virus.

Malignant lymphomas were observed in 38% (9 of 24) of simian immunodeficiency virus (SIV)-infected cynomolgus monkeys (Macaca fascicularis) 5 to 15 months after inoculation with SIV strain SMM3. Lymphomagenesis in the SIV-infected monkeys was not related directly to the SIV-infectious dose given. All SIV-infected animals developed severe immunodeficiency. No significant difference in immunodeficiency was observed between tumor-bearing and non-tumor-bearing animals. In contrast, no lymphomas were observed in a comparable group of HIV-2-infected monkeys, which did not develop immunodeficiency; nor did the noninfected control monkeys. All 9 SIV-related tumors were high-grade B-cell lymphoblastic or pleomorphic lymphomas with extranodal, disseminated growth. Most tumors showed marked infiltration by monocytes and CD8+ T lymphocytes. Occasional tumor infiltrating cells showed immunohistochemical reaction for SIV. The cells of two tumors were established in vitro and shown to be of B-cell phenotype. The tumor cell cultures showed no reverse transcriptase activity and no evidence of virus infection by electron microscopy. Our observations indicate that SIV-induced immunodeficiency in cynomolgus monkeys also mimics HIV infection and AIDS in humans with regard to increased lymphomagenesis and type of lymphomas.

Animals↗
PubMed1989

Predictive markers of AIDS: a follow-up of lymphocyte subsets and HIV serology in a cohort of patients with lymphadenopathy.

From 1982 to 1985, 89 HIV-1 seropositive men with persistent generalized lymphadenopathy (PGL) were enrolled into a prospective longitudinal study. In February 1988, after a mean observation time of 45 months, 23 patients had progressed to AIDS with opportunistic infection (AIDS/OI), 4 had developed Kaposi's sarcoma, 47 had developed HIV-related symptoms, 14 still had PGL as only symptom, and 1 was lost to follow-up. Patients with CD4 lymphocytes less than or equal to 0.40 x 10(9)/l as well as patients with HIV antigenaemia and those lacking antibodies to p24 all had a significantly higher risk of developing AIDS/OI within 30 months of observation than other patients. HIV antigen was present in 70% and antibodies to p24 were lacking in 61% of the patients at the time of AIDS/OI diagnosis. All but one (96%) of the AIDS/OI patients had CD4 numbers less than or equal to 0.20 x 10(9)/l at the same time. The estimated median time to AIDS/OI in patients with HIV antigenaemia was 21 months and in patients lacking p24 antibodies 27 months. In patients with CD4 numbers less than or equal to 0.20 and 0.40 x 10(9) cells/l the estimated median time to AIDS/OI was 14 months and longer than 30 months, respectively.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with HIV-2.

Ten healthy adult cynomolgus monkeys (Macaca fascicularis) were inoculated with two different isolates of human immunodeficiency virus type 2 (HIV-2), SBL-6669 and SBL-K135, to establish an animal model for HIV infection. HIV-2SBL-6669 had been propagated for a long time in continuous human cell lines whereas HIV-2SBL-K135 had been grown only in fresh human and monkey lymphocyte cultures or previously for a short time in a continuous cell line. Virus was isolated from three or four animals inoculated with HIV-2SBL-K135 but in none of six monkeys inoculated with HIV-2SBL-6669. All animals seroconverted although the antibody response was higher in SBL-K135 virus-infected monkeys. Varying degrees of lymphadenopathy were observed but there were no significant changes in the numbers of CD4+ and CD8+ T cells. The infection was transferred to two monkeys inoculated with blood from a previously SBL-K135 virus-infected monkey. Four animals inoculated with HIV-2SBL-K135, which had never been propagated in continuous human cell lines, showed strong antibody responses against both gag- and env- encoded proteins of HIV-2. None of the SBL-6669 infected monkeys showed antibodies to core proteins. HIV-2 infection of cynomolgus monkeys represents a useful experimental model for HIV vaccine trials and antiviral testing.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with simian immunodeficiency virus (SIVsm).

Five healthy cynomolgus monkeys were inoculated intravenously with simian immunodeficiency virus (SIVsm) propagated in human lymphocytes. All five animals became infected. Virus was recovered from blood mononuclear cells and viral antigen was detected in serum 12 days postinoculation (PI) in all inoculated animals. Virus was also isolated in all five animals tested 74 to 226 days PI. Antibodies to different structural proteins of SIV and HIV-2 were demonstrated by ELISA, Western blot, and radioimmunoprecipitation assay from day 31 PI concomitantly with a reduction of viral proteins in the serum. Reappearance of antigen accompanied by a fall in antibody to gag products (p26) was observed in two monkeys 69 days PI. All SIV-infected monkeys showed a pronounced decrease in CD4+ lymphocytes demonstrable already 12 days PI. They also developed persistent lymphadenopathy. Thus, infection of cynomolgus monkeys with SIVsm mimics events in human immunodeficiency virus infection in humans but the course of evolution of pathogenic events in the monkey is markedly compressed. This experimental model will be useful for evaluation of HIV vaccines and antiviral testing.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Immunoglobulin allotypes are normally distributed in Swedish AIDS patients.

Immunoglobulin allotypes G1m(a), G1m(x), G3m(b) and Km(1) were determined in 83 Swedish AIDS patients. Twenty of the patients had Kaposi's sarcoma and 29 had Pneumocystis carinii pneumonia. The distribution of the Gm and Km allotypes did not significantly differ between these different disease categories and the general Swedish population.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Group specific component and susceptibility to HIV infection and progression to AIDS.

The distribution of phenotypes of the group specific component (Gc) was examined in 85 AIDS patients and in 40 couples, each consisting of one HIV seropositive patient and one seronegative sexual partner. Phenotype and allele frequencies in these groups did not differ significantly from those in a Swedish control population. Our observations did not indicate any involvement of the Gc system in susceptibility to HIV infection or progression to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Genetic and environmental determination of human sleep.

Self-reported sleep data from 2238 monozygotic and 4545 dizygotic adult twin pairs indicated a significant hereditary effect on sleep length [overall heritability estimate (h2 = 0.44)] and on sleep quality (h2 = 0.44). When the data were examined in subgroups defined by sex, age (18-24 years and 25 or more years of age), and cohabitation status of the twin pair, the highest heritability estimates for sleep length were for twins living together aged 25 or older. For twins living apart the heritability estimates were statistically significant in all women and men aged 25 or older. For sleep quality significant heritability estimates were found for all groups except women living together.

Adolescent↗
PubMedDate not supplied

Monocyte/macrophage giant cell disease in SIV-infected cynomolgus monkeys.

A non-opportunistic, generalized giant cell disease (GCD) was found in 12 out of 25 (48%) cynomologus monkeys infected with SIVsm. Most organs were affected notably the lymph nodes (LN), spleen, gut, liver, lungs and CNS. The multinucleated GC varied considerably in cell size and in the number and cytoplasmic distribution of the nuclei. Immunohistochemically most GC expressed SIV antigens and markers of mononuclear phagocytes (CD68), CD4 and also occasionally the T-cell markers CD45RO, CD43 and CD2. Monkeys with GCD had more pronounced immunosuppression with lower CD4-cell counts, more often demonstrable SIV antigen in the blood and LN and had been infected for a longer time period, as compared to monkeys without GCD. These findings show that SIV infection in cynomolgus monkeys is frequently associated with extensive formation of multinucleated GC of macrophage origin, which appears to be related to the pathogenesis of the infection and the degree of immunosuppression.

Animals↗
PubMedDate not supplied

Accessory cells and macrophages in the histopathology of SIVsm-infected cynomolgus monkeys.

Thirty-three out of 39 cynomolgus monkeys (Macaca fascicularis) infected with SIVsm (strain SMM-3) developed various pathologies similar to those seen in human AIDS. Lymphadenopathy was frequently seen (72%) and was characterized by hyperplasia followed by involution of follicle/germinal centres due to follicular dendritic cell (FDC) destruction corresponding to the degree of immunodeficiency. Various organs such as the lungs, liver, central nervous system, kidneys, gastrointestinal tract, cardiovascular system and adrenals showed histopathological changes with prominent monocyte/macrophage and multinucleated giant cell formation. Eighteen (54%) monkeys presented with extranodal malignant lymphoma (ML) associated with marked CD4 decrease and destruction of follicular architecture. The high frequency of ML, giant cell disease and lymph node changes seen in the present SIV model provides an attractive system to elucidate the role of FDC and monocytes/macrophages in the pathogenesis of these conditions in common with HIV infection and human AIDS.

Animals↗
PubMedDate not supplied

Efficacy of inactivated whole HIV-2 vaccines with various adjuvants in cynomolgus monkeys.

Twenty-one cynomolgus monkeys were immunized with whole inactivated HIV-2 preparations administered with various adjuvants (incomplete Freund's adjuvant, Alum, Ribi, MDP, or Iscoms) and challenged with 10 or 100 MID50 of a homologous monkey-cell grown, cell-free HIV-2. Seven animals were completely protected against infection, three showed reduced virus replication. The vaccines elicited neutralizing and ADCC antibodies; the titers did not correlate with protection. Immunization with a whole inactivated vaccine can protect primates from intravenous challenge with a monkey-cell grown cell-free human immunodeficiency virus type 2.

AIDS Vaccines↗
PubMedDate not supplied

A formalin inactivated whole SIVmac vaccine in Ribi adjuvant protects against homologous and heterologous SIV challenge.

Eight monkeys were immunized at 0, 4, 9, and 18 weeks with a total of 2 mg of formalin inactivated SIVmac vaccine with Ribi adjuvant. Two weeks after the last booster four immunized monkeys and two controls were challenged with 10 MID50 of live homologous virus SIVmac, and the remaining four vaccinated animals along with two controls were challenged with the heterologous SIVsm strain. All eight vaccinated monkeys resisted the virus challenge, whereas all controls became infected. Three months after the first challenge the monkeys were rechallenged with the same virus strain, without further boosting. Two of four vaccinated monkeys were still resistant to the homologous SIV strain, and three of four monkeys were resistant to the heterologous SIVsm strain. This study demonstrates vaccine induced cross-protection between SIV strains.

Adjuvants, Immunologic↗