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Biomedical subjects

V Liska

Publications and source records attributed to V Liska.

At least 19 recordsLinked to original sources
PubMed2001

Passive immunization against oral AIDS virus transmission: an approach to prevent mother-to-infant HIV-1 transmission?

To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge.

To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV) transmission, we established a simian-human immunodeficiency virus (SHIV) infection model in neonatal macaques that mimics intrapartum mucosal virus exposure (T. W. Baba et al., AIDS Res. Hum. Retroviruses 10:351-357, 1994). Using this model, neonates were protected from mucosal SHIV-vpu(+) challenge by pre- and postnatal treatment with a combination of three human neutralizing monoclonal antibodies (MAbs), F105, 2G12, and 2F5 (Baba et al., Nat. Med. 6:200-206, 2000). In the present study, we used this MAb combination only postnatally, thereby significantly reducing the quantity of antibodies necessary and rendering their potential use in humans more practical. We protected two neonates with this regimen against oral SHIV-vpu(+) challenge, while four untreated control animals became persistently infected. Thus, synergistic MAbs protect when used as immunoprophylaxis without the prenatal dose. We then determined in vitro the optimal MAb combination against the more pathogenic SHIV89.6P, a chimeric virus encoding env of the primary HIV89.6. Remarkably, the most potent combination included IgG1b12, which alone does not neutralize SHIV89.6P. We administered the combination of MAbs IgG1b12, 2F5, and 2G12 postnatally to four neonates. One of the four infants remained uninfected after oral challenge with SHIV89.6P, and two infants had no or a delayed CD4(+) T-cell decline. In contrast, all control animals had dramatic drops in their CD4(+) T cells by 2 weeks postexposure. We conclude that our triple MAb combination partially protected against mucosal challenge with the highly pathogenic SHIV89.6P. Thus, combination immunoprophylaxis with passively administered synergistic human MAbs may play a role in the clinical prevention of mother-to-infant transmission of HIV type 1.

Administration, Oral↗
PubMed2000

Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain reaction to quantify SIV RNA load: comparison of one- versus two-enzyme systems.

Plasma viral RNA load is a key parameter in disease progression of lentiviral infections. To measure simian immunodeficiency virus (SIV) RNA loads, we have established a quantitative one-tube assay based on TaqMan chemistry. This real-time reverse transcriptase-polymerase chain reaction (RT-PCR) has advantages compared with previous methods, such as higher sensitivity, shorter time consumption, and low risk of cross-contamination. The sensitivity of the assay was optimized by comparing different enzyme systems. The one-enzyme protocol using rTth DNA polymerase was superior to two assays employing two enzymes. It detects 100% of the samples containing four copies of RNA transcript and allows quantification of viral RNA loads over an 8-log unit dynamic range. As few as 50 copies per milliliter of plasma can be detected within RNA extracted from 140 microl of plasma. This is especially relevant in studies employing neonatal macaques, from which only small volumes of blood can be sampled, and in studies in which low viral RNA loads are expected. Because of the use of rTth DNA polymerase, DNA contamination can be avoided by carryover prevention with uracil N-glycosylase (UNG). We demonstrate that for optimization of real-time PCR sensitivity, not only concentrations of different reagents but also different enzyme systems must be evaluated. Our assay facilitates and enhances the quantification of plasma RNA loads, a critical parameter for many studies, including evaluations of vaccine candidates or antiviral regimens.

Animals↗
PubMed2000

Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection.

Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu+ (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV-vpu+ completely in vitro through synergistic interaction. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.

Animals↗
PubMed1999

Viremia and AIDS in rhesus macaques after intramuscular inoculation of plasmid DNA encoding full-length SIVmac239.

We have succeeded in stably maintaining the entire genome of SIVmac239 as a plasmid clone. Supercoiled proviral plasmid DNA was inoculated intramuscularly into two adult rhesus macaques and into a neonate. All three animals became viremic and seroconverted. Viral kinetics were followed prospectively by quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT-PCR), measurement of proviral DNA load in peripheral blood mononuclear cells (PBMCs) by PCR, and virus isolation by cocultivation. The infant developed high virus loads and succumbed to AIDS and SIV-associated nephropathy at 10 weeks postinoculation. Both adults are still living but have progressed to AIDS; one adult has also developed severe thrombocytopenia. We conclude that infection through intramuscular inoculation of cloned plasmid DNA encoding the entire proviral genome is reproducible and will provide a useful tool for studying viral pathogenesis.

Animals↗
PubMed1999

Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques.

A substantial risk in using live attenuated, multiply deleted viruses as vaccines against AIDS is their potential to induce AIDS. A mutant of the simian immunodeficiency virus (SIV) with large deletions in nef and vpr and in the negative regulatory element induced AIDS in six of eight infant macaques vaccinated orally or intravenously. Early signs of immune dysfunction were seen in the remaining two offspring. Prolonged follow-up of sixteen vaccinated adult macaques also showed resurgence of chronic viremia in four animals: two of these developed early signs of disease and one died of AIDS. We conclude that this multiply deleted SIV is pathogenic and that human AIDS vaccines built on similar prototypes may cause AIDS.

Aging↗
PubMed1999

Oral transmission of primate lentiviruses.

Oral transmission of human immunodeficiency virus type 1 (HIV-1) is well documented in children who become infected postnatally through breast milk. In contrast, epidemiologic surveys have yielded conflicting data regarding oral HIV-1 transmission among adults, even though case reports have described seroconversion and the development of AIDS in adults whose only risk was oral-genital contact. To study oral virus transmission in primate models, we exposed rhesus macaques of various ages to cell-free simian immunodeficiency virus (SIV), including uncloned and molecularly cloned viruses. In neonates, viremia and AIDS developed after nontraumatic oral exposure to several SIV strains. Furthermore, chimeric simian human immunodeficiency viruses containing the HIV-1 envelope can also cross intact upper gastrointestinal mucosal surfaces in neonates. In adult macaques, infection and AIDS have resulted from well-controlled, nontraumatic, experimental oral exposure to different strains of SIV. These findings have implications for the risks of HIV-1 transmission during oral-genital contact.

Age Factors↗
PubMed1999

Persistent infection of rhesus macaques by the rev-independent Nef(-) simian immunodeficiency virus SIVmac239: replication kinetics and genomic stability.

We generated previously a Nef(-), replication-competent clone of SIVmac239 in which the Rev protein and the Rev-responsive element were replaced by the constitutive transport element (CTE) of simian retrovirus type 1 (A. S. von Gegerfelt and B. K. Felber, Virology 232:291-299, 1997). In the present report, we show that this virus was able to infect and replicate in rhesus macaques. The Rev-independent Nef(-) simian immunodeficiency virus induced a persistent humoral immune response in all monkeys, although viral loads were very low. Upon propagation in the monkeys, the genotype remained stable and the virus retained its in vitro growth characteristics. The infected monkeys showed normal hematological values and no signs of disease at more than 18 months post-virus exposure. Therefore, replacement of the essential Rev regulation by the CTE generated a virus variant that retained its replicative capacity both in vitro and in vivo, albeit at low levels.

Animals↗
PubMed1999

[Contrast sensitivity in type I diabetics without symptoms of diabetic retinopathy].

UNLABELLED: The objective of the work was to assess whether in patients with IDDM without signs of diabetic retinopathy changes in the sensitivity function to contrast (CS) develop as compared with a group of healthy subjects matched for age but also as a result of the persistence of IDDM or the level of its long-term compensation investigated by means of glycated haemoglobin (HbA1c). CS was examined by the static method using a VCTS 6500 table from a distance of 208 and 420 cm which covered the spatial frequencies from 1.15 to 27.25 c/st. Moreover the authors assessed the best correctable central visual acuity on Snellen's optotypes, the ophthalmoscopic finding on the fundus with a colour photograph, fluorescein angiography and the HbA1c serum level. A group of 49 patients with IDDM was divided into two age groups: A(under 35 years), B (35 years and above). A marked decline of the CS function occurs in all spatial frequencies in both age groups. On comparison of the persistence of IDDM in group B no significant difference was found in CS, while in group A statistical significance was revealed in spatial frequencies 4 and 27.25 c/st. On comparison of the CS function in diabetics with a normal and pathological HbA1c level it was found that long-term hyperglycaemia has not a marked effect on visual functions. CONCLUSION: The decline of CS in patients with IDDM without signs of diabetic retinopathy is influenced in particular by the patient's age, in junior patients also by the persistence of IDDM. Examination of the CS is a simple non-invasive method suitable for screening of early affections of the eyes in IDDM.

Adult↗
PubMed1999

Are contrast sensitivity functions impaired in insulin dependent diabetics without diabetic retinopathy?

PURPOSE: To confirm the influence of multilevel metabolic disturbance of insulin dependent diabetes mellitus (IDDM) on the vision even before the onset of the other changes routinely evaluated by ophthalmologists. METHODS: Contrast sensitivity functions (CSFs) were estimated using the VCTS 6500 board. The standardised measurement procedure was performed. The value of the threshold contrast sensitivity was obtained for five spatial frequencies (1.5-3-6-12-18 c/deg). Other data was collected (duration of diabetes, BCVA, funduscopy, fluoresceine angiography, HbA1C). The study group consisted of 48 IDDM patients (94 eyes) without diabetic retinopathy and with Snellen BCVA > 1.0. The control group (56 normals, 98 eyes) was age and BCVA matched. RESULTS: Highly statistically significant decrease of the CSFs in all spatial frequencies in the study group was obtained. Correlation between duration of the diabetes and impaired degree of CSFs was present in the middle spatial frequency. No significant changes in CSFs were found among patients with pathological value of glycated hemoglobin HbA1c (> 7.8%). CONCLUSIONS: If compared with routinely used Snellen visual acuity, the CSFs are more complex descriptors of the subjects vision abilities. IDDM has an influence on these sensitive functions, especially during examination in the middle spatial frequency of 6 and 12 c/deg, before disturbing visual acuity and before changes in the retinal morphology. Decrease of CSFs was influenced mainly by the patients' age and partially (in the middle spatial frequency) by the IDDM duration.

Adult↗
PubMed1998

Oral SIV, SHIV, and HIV type 1 infection.

Several strains of simian immunodeficiency virus (SIV), including uncloned and molecularly cloned SIV strains, can cross intact mucosal surfaces after oral exposure in both adult and neonatal rhesus macaques, resulting in viremia and disease. Cell-free SIV strains as well as infected whole blood have resulted in systemic infection after oral inoculation. Neonatal macaques, exposed orally to the chimeric SHIV-vpu+, a derivative of SIVmac239 that encodes the env gene of the T cell-tropic HIV-IIIB, have also become persistently infected. These data indicate that oral exposure to various virus strains, including T cell-tropic variants, leads to infection. After nontraumatic inoculation, the oral route was more efficient than the rectal route in permitting SIV entry in adult macaques. Infection and AIDS resulting from oral exposure of adult macaques have implications for the transmission of the human immunodeficiency virus type 1 (HIV-1) during oral-genital contact.

AIDS Vaccines↗
PubMed1998

[Contrast sensitivity in glaucoma and ocular hypertension].

It is known that contrast sensitivity declines with advancinG age and during different ophthalmological diseases. The authors examined 263 eyes of 141 patients with different types of glaucoma and 213 eyes of 107 patients with ocular hypertension. The patients were divided into two groups by age: A = under 60 years (mean 53.2 in glaucoma, 51.1 in OH) and B = 60 years and above (mean 67.5 in glaucoma and 65.6 in OH). For examination of contrast sensitivity the authors used a VCTS 6500 board from a 3 m distance, the visual field was examined by means of Goldman's kinetic perimeter or a static Optifield II perimeter and the discs of the optic nerve were examined biomicroscopically or a photograph of the disc was taken. Impaired contrast sensitivity was found in group A in 71.7% of glaucoma patients and in 61.6% in ocular hypertension. In group B in 81.7% glaucoma patients and in 75.1% of patients with ocular hypertension. The authors also proved an association between the decline of contrast sensitivity and impairment of the perimeter and enlargement of the glaucoma excavation of the optic disc. The authors recommend examination of the contrast sensitivity as a supplementary method for screening and observation of ocular hypertension and glaucoma.

Aged↗
PubMed1997

Detection of simian T cell leukemia virus type I infection in seronegative macaques.

Simian species of Asian and African origin are naturally infected with the simian T cell leukemia virus type I (STLV-I). Like the closely related human T cell leukemia virus type I (HTLV-I), STLV-I is primarily cell associated, and typical infections exhibit low viral burdens. Four macaques experimentally inoculated with a new STLV-I strain isolated from a sooty mangabey monkey were examined over extended periods of time for signs of infection by (1) commercial enzyme immunoassay and immunoblot assay for cross-reactive serum antibodies to HTLV-I, (2) commercial HTLV-I p24gag antigen-capture assay on supernatants from cocultures of macaque peripheral blood mononuclear cells (PBMCs) with human PBMCs, and (3) nested PCR amplification of proviral sequences in macaque PBMC DNA. The nested PCR assay was 100% specific and detected a single STLV-I copy in 150,000 PBMCs. In addition, our data show that experimental infection of macaques with STLV-I can be serologically silent for more than 43 months.

Animals↗
PubMed1997

Simultaneous detection of simian retrovirus type D serotypes 1, 2, and 3 by polymerase chain reaction.

Asymptomatic infection of macaques with macaques with simian retroviruses type D (SRV/D), the etiologic agents of one form of retrovirus-induced simian immunodeficiency disease, can confound experiments with the simian immunodeficiency virus (SIV), which also induces immunodeficiency disease in macaques. The SIV/macaque model is the preferred nonhuman primate model for AIDS-related research. Serological screening for SRV/D alone is insufficient because not all infected animals seroconvert, and virus isolation by cocultivation may require 4 to 6 weeks. We have established a DNA polymerase chain reaction (PCR) assay. One set of nested primers allows detection of SRV/D serotypes 1, 2, and 3 and distinguishes SRV-2 from the other two serotypes. The PCR assay is sensitive; a single proviral copy of SRV/D could be detected in 150,000 to 210,000 macaque peripheral blood mononuclear cells (PBMCs). When applied to a panel of virus isolation-positive macaque samples, the PCR assay was positive in 100% of the tests. No false-positive results were seen when known specific-pathogen-free (SPF) macaques were examined. We propose that macaques be screened with a combination of SRV/D serology and this DNA PCR assay prior to enrollment in experiments with SIV.

Animals↗
PubMed1997

[Marfan syndrome].

The author describes three forms of Marfan's syndrome which have only the skeletal symptoms in common. In all instances also ophthalmological symptoms are present but of different types. A familial case was observed only in one family; in the remaining two frust forms of Marfan's syndrome are involved.

Adult↗
PubMed1996

Infection and AIDS in adult macaques after nontraumatic oral exposure to cell-free SIV.

Unprotected receptive anal intercourse is a well-recognized risk factor for infection with human immunodeficiency virus-type 1 (HIV-1). Isolated human case reports have implicated HIV-1 transmission by oral-genital exposure. Adult macaques exposed nontraumatically to cell-free simian immunodeficiency virus (SIV) through the oral route became infected and developed acquired immunodeficiency syndrome (AIDS). The minimal virus dose needed to achieve systemic infection after oral exposure was 6000 times lower than the minimal dose required to achieve systemic infection after rectal exposure. Thus, unprotected receptive oral intercourse, even in the absence of mucosal lesions, should be added to the list of risk behaviors for HIV-1 transmission.

Animals↗