Showing papers on "Viremia published in 1996"

Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma

Abstract: The relation between viremia and clinical outcome in individuals infected with human immunodeficiency virus-type 1 (HIV-1) has important implications for therapeutic research and clinical care. HIV-1 RNA in plasma was quantified with a branched-DNA signal amplification assay as a measure of viral load in a cohort of 180 seropositive men studied for more than 10 years. The risk of acquired immunodeficiency syndrome (AIDS) and death in study subjects, including those with normal numbers of CD4+ T cells, was directly related to plasma viral load at study entry. Plasma viral load was a better predictor of progression to AIDS and death than was the number of CD4+ T cells.

Viral dynamics in hepatitis B virus infection

Abstract: Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximately 10 day, which implies a 50% daily turnover of the free virus population Total viral release into the periphery is approximately 10(11) virus particles per day Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV Most strikingly, there is no indication of drug resistance in HBV-infected patients treated for up to 24 weeks

Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1.

Abstract: Background Activation of the immune system is a normal response to antigenic stimulation, and such activation enhances the replication of human immunodeficiency virus type 1 (HIV-1). We studied the effect of immunization with a common recall antigen on viral expression in HIV-1–infected patients, on the ability to isolate virus, and on the susceptibility to HIV-1 infection of peripheral-blood mononuclear cells (PBMCs) from control subjects not infected with HIV-1. Methods Thirteen HIV-1–infected patients and 10 uninfected adults were given a 0.5-ml booster dose of tetanus toxoid. Studies were performed to evaluate changes in the degree of plasma viremia, proviral burden, the ability to isolate HIV-1, and the susceptibility of PBMCs to acute infection in vitro. Two patients underwent sequential lymph-node biopsies for the assessment of viral burden in these tissues. Results All 13 HIV-1–infected patients had transient increases in plasma viremia after immunization, and the proviral burden increased in 11. ...

Immunopathogenesis of HIV infection.

Abstract: The rate of progression of HIV disease may be substantially different among HIV-infected individuals. Following infection of the host with any virus, the delicate balance between virus replication and the immune response to the virus determines both the outcome of the infection, i.e. the persistence versus elimination of the virus, and the different rates of progression. During primary HIV infection, a burst of viremia occurs that disseminates virus to the lymphoid organs. A potent immune response ensues that substantially, but usually not completely, curtails virus replication. This inability of the immune system to completely eliminate the virus leads to establishment of chronic, persistent infection that over time leads to profound immunosuppression. The potential mechanisms of virus escape from an otherwise effective immune response have been investigated. Clonal deletion of HIV-specific cytotoxic T-cell clones and sequestration of virus-specific cytotoxic cells away from the major site of virus replication represent important mechanisms of virus escape from the immune response that favor persistence of HIV. Qualitative differences in the primary immune response to HIV (i.e. mobilization of a restricted versus broader T-cell receptor repertoire) are associated with different rates of disease progression. Therefore, the initial interaction between the virus and immune system of the host is critical for the subsequent clinical outcome.

Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara.

Abstract: The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. High-level primary plasma viremia with subsequently increasing viremia was associated with rapid progression to AIDS (n = 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associated with progression to AIDS within a year (n = 6). Low levels of primary plasma viremia followed by sustained restriction of virus replication were associated with maintenance of normal lymphocyte subsets and intact lymphoid architecture (n = 4), reminiscent of the profile observed in human immunodeficiency virus type 1-infected long-term nonprogressors. Three of four macaques that showed this pattern had been immunized with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and extent of virus replication to disease course and suggest that sustained suppression of virus promotes long-term, asymptomatic survival of SIV-infected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequent disease course, even if sterilizing immunity is not achieved.

An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys.

Abstract: To explore the roles played by specific human immunodeficiency virus type 1 (HIV-1) genes in determining the in vivo replicative capacity of AIDS viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys following infection with two chimeric simian/human immunodeficiency viruses (SHIVs). These viruses were composed of simian immunodeficiency virus SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rep. Virus replication was assessed during primary infection of rhesus monkeys by measuring plasma SIVmac p27 levels and by quantifying virus replication in lymph nodes using in situ hybridization. SHIV-HXBc2, which expresses the HIV-1 env of a T-cell-tropic, laboratory-adapted strain of HIV-1 (HXBc2), replicated well in rhesus monkey peripheral blood leukocytes (PBL) in vitro but replicated only to low levels when inoculated in rhesus monkeys. In contrast, SHIV-89.6 was constructed with the HIV-1 env gene of a T-cell- and macrophage-tropic clone of a patient isolate of HIV-1 (89.6). This virus replicated to a lower level in monkey PBL in vitro but replicated to a higher degree in monkeys during primary infection. Moreover, monkeys infected with SHIV-89.6 developed an inversion in the PBL CD4/CD8 ratio coincident with the clearance of primary viremia. The differences in the in vivo consequences of infection by these two SHIVs could not be explained by differences in the immune responses elicited by these viruses, since infected animals had comparable type-specific neutralizing antibody titers, proliferative responses to recombinant HIV-1 gp120, and virus-specific cytolytic effector T-cell responses. With the demonstration that a chimeric SHIV can replicate to high levels during primary infection in rhesus monkeys, this model can now be used to define genetic determinants of HIV-1 pathogenicity.

Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice.

Abstract: To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually intact, and the infection is initially controlled in most organ sites including the blood. However, approximately 2 mo postinfection, CTL memory cannot be detected, and recrudescence of viremia to titers as high as seen during the acute phase of the infection is observed. To investigate whether this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient virus control was observed in most mice. However, approximately 3 mo postinfection, blood virus titers were as high as observed during the acute infection, and no CTL memory could be demonstrated. These results indicate that Abs and/or B cells are required for permanent virus control and that in their absence, the virus-specific CTL potential becomes exhausted. Together our results indicate that while CD8+ cells play a dominant role in acute virus control, all three major components of the immune system are required for long term virus control.

Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses

Abstract: A commercially available immunoglobulin G (IgG) from horses, hyperimmunized to Ebola virus, was evaluated for its ability to protect cynomolgus monkeys against disease following i.m. inoculation with 1 000 PFU Ebola virus (Zaire '95 strain). Six monkeys were treated immediately after infection by i.m. infection of 6.0 ml IgG; these animals developed passive ELISA titers of 1:160 to 1:320 to Ebola, two days afer inoculation. However, the beneficial effects of IgG treatment were limited to a delay in onset of viremia and clinical signs, in comparison with untreated controls. The six IgG recipients had no detectable viremia day 5, in contrast with three virus infected controls whose viremias exceeded 7.0 log10 PFU/ml that day. The controls died on days 6, 6, and 7, while two IgG recipients died day 7 and the remaining 4 died day 8, all with high viremias. These results document that passively acquired antibody can have a beneficial effect in reducing the viral burden in Ebola-infected primates; however, effective treatment of human patients may require antibodies with higher specific activities and more favorable pharmacokinetic properties than the presently available equine IgG.

Kinetics of humoral immune response to the major structural proteins of the porcine reproductive and respiratory syndrome virus.

Abstract: The kinetics of appearance of antibodies directed to the major structural proteins N, M and E of porcine reproductive and respiratory syndrome virus (PRRSV) was followed in pigs naturally- and experimentally-exposed to the virus. Specific IgM antibody titers were first detected by indirect immunofluorescence (IIF) at the end of the first week of PRRSV infection, peaked by day 14 to 21 post-inoculation (p.i.), then rapidly decreased to undetectable levels by day 35 to 42 p.i. On the other hand, specific IgG antibody titers peaked by day 21 to 28 p.i. and remained unchanged to the end of the 6- or 9-week observation period; in addition, a persistent viremia was observed. Virus neutralizing (VN) antibody titers >8 were not detected until 3 to 4 weeks p.i. Taken together, the results obtained by Western blotting analyses using purified virus andE. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i.

West Nile virus neuroinvasion and encephalitis induced by macrophage depletion in mice.

Abstract: The encephalitic West Nile virus and its nonneuroinvasive variant, WN-25, were used to study the effect of macrophage depletion on viral invasion of the central nervous system. The in vivo elimination of macrophages was achieved by use of liposome-encapsulated drug dichloromethylene diphosphonate. Depletion of macrophages had an exacerbating effect on the course of the viral infection, exhibited by higher and extended viremia and accelerated development of encephalitis and death. Using a low dose of West Nile virus (5 PFU/mouse), an increase in mortality (from 50% to 100%) due to macrophage depletion was demonstrated. Furthermore, the attenuated noninvasive variant WN-25 showed high and prolonged viremia in the macrophage depleted mice (≈5 log 10 PFU/ml versus 2 in control mice), that allowed the penetration of the virus into the central nervous system. The mortality rate caused by the attenuated virus in the macrophage-depleted mice was 70–75%, as compared to complete survival in the control inoculated mice. These results indicate a significant role of macrophages in the non-specific immediate defence system of the organism in case of viral infection.

Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation

Abstract: During peak viremia and initial antibody response, rhesus macaques infected with pathogenic and nonpathogenic isolates of SIV show distinct differences in viral load and tissue distribution. Animal...

Infection of primary human microglia and monocyte-derived macrophages with human immunodeficiency virus type 1 isolates: evidence of differential tropism.

Abstract: To ascertain whether viruses present at the time of primary viremia can infect the central nervous system and to determine if microglial tropism is distinct from tropism for monocyte-derived macrophages (MDM), 27 human immunodeficiency virus type 1 (HIV-1) isolates obtained from acutely infected individuals, as well as laboratory strains, were assayed for their ability to replicate in primary adult microglial cultures and in MDM. Most of the isolates replicated equally well in both microglia and MDM, but several isolates replicated preferentially in one of the two cell types, differing by as much as 40-fold in p24gag production. This indicated that while MDM and microglial tropism overlap, a subset of isolates is particularly tropic for one of the two cell types. One isolate was further adapted to microglia by 15 sequential passages, raising the peak p24 concentration produced by 1,000-fold. In addition, the passaged virus induced marked cytopathologic changes (vacuolization and syncytium formation) in infected microglial cultures. Sequence comparison of the V3 loop of unpassaged and multiply passaged virus revealed amino acid changes shown to be associated with isolates from patients with HIV dementia. Our data support the hypothesis that HIV-1 infection can be established in the central nervous system by viruses present early in HIV infection, that some of these viruses are particularly tropic for microglia, and that adaptation in this cell type can result in the selection of a pool of predominantly microglia-tropic (neurotropic) viruses.

Clonal expansion of infected cells: a way of life for HTLV-I.

Abstract: Human T-cell lymphotropic virus type I (HTLV-I) is characterized by a remarkable genetic stability and high proviral loads in the absence of malignant disease. This results from the effect of tax on cell cycling. The virus replicates essentially in concert with the cell that is, via mitosis, which can be shown by polymerase chain reaction amplification of the HTLV-I integration sites. This is true of all stages of HTLV-I infection and accompanies adult T-cell leukemia/lymphoma. The very low viremia results from its genetic organization.

9-[2-(Phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques.

Abstract: The long-term therapeutic and toxic effects of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) were evaluated in simian immunodeficiency virus (SIV)-infected newborn rhesus macaques. Four untreated SIV-infected newborn macaques developed persistently high levels of viremia, and three of the four animals had rapidly fatal disease within 3 months. In contrast, long-term PMPA treatment of four newborn macaques starting 3 weeks after virus inoculation resulted in a rapid, pronounced, and persistent reduction of viremia in three of the four animals. Emergence of virus with fivefold-decreased susceptibility to PMPA occurred in all four PMPA-treated animals and was associated with the development of a lysine-to-arginine substitution at amino acid 65 (K65R mutation) and additional mutations in the reverse transcriptase; however, the clinical implications of this low-level drug resistance are nuclear. No toxic side effects have been seen, and all PMPA-treated animals have remained disease-free for more than 13 months. Our data suggest that PMPA holds much promise for the treatment of human immunodeficiency virus-infected human infants and adults.

Persistent Hepatitis C Viremia Predicts Late Relapse after Sustained Response to Interferon-α in Chronic Hepatitis C

Abstract: Objective: To define long-term outcome in patients with chronic hepatitis C who remain viremic after sustained biochemical response to interferon-α therapy. Design: Prospective evaluation of an out...

Suppression of HIV replication by lymphoid tissue CD8+ cells correlates with the clinical state of HIV-infected individuals

Abstract: Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject’s peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results add further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

HIV-specific cellular and humoral immune responses in primary HIV infection.

Abstract: Primary human immunodeficiency virus (HIV) infection is characterized by a high-titer viremia that declines precipitously within weeks, most likely as a result of host immune responses. Peripheral blood mononuclear cells (PBMCs) and plasma of four recently HIV-infected individuals were examined to assess the humoral and cellular immune responses potentially involved in early suppression of viral replication. Neutralizing antibodies against autologous viral isolates were low or undetectable in three subjects studied. Cellular cytotoxicity was assayed using Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (B-LCLs) infected with recombinant vaccinia that express HIV-1 proteins. HIV envelope-specific cytotoxicity, which was not mediated by CD8+ cells nor human leukocyte antigen (HLA) class I restricted, developed in PBMCs of all four subjects early after primary infection, but was not correlated with declines in viremia. Gag-specific cytotoxic T lymphocyte (CTL) activity was observed in freshly isolated PBMCs of two subjects, and HIV-specific CTL cell lines were cultured from PBMCs of three subjects shortly after HIV infection. Antibody-dependent cellular cytotoxicity (ADCC) developed early in all four subjects, and was temporally correlated with declines in viremia in two subjects in whom viral load was well characterized. These data suggest that both CTL responses and ADCC may be critical to control of viral replication in acute HIV infection.

Factors Influencing Human Immunodeficiency Virus Type 1 Transmission by Blood Transfusion

Abstract: One hundred thirty-two recipients of blood components that retrospectively tested positive for antibody to human immunodeficiency virus type 1 (anti-HIV-1) were identified. Fourteen (11%) remained seronegative throughout follow-up. Donor and recipient characteristics that could have influenced transmission were examined. Attributes did not differ for infected and uninfected recipients. Peripheral blood mononuclear cells (PBMC) from uninfected recipients were HIV-1-negative by DNA amplification and culture but were susceptible to in vitro infection. Transmitting and nontransmitting donors at donation differed only for HIV-1 RNA positivity. By immunocapture reverse transcriptase-polymerase chain reaction, 6 of 11 transmitters and 0 of 11 nontransmitters tested RNA-positive (P = .02). A more sensitive quantitative RNA assay detected RNA in all donation sera, but median levels were higher in transmitting than nontransmitting sera (P = .01). Median CD4 cell counts were lower for transmitting than nontransmitting donors at enrollment (P = .02). Level of viremia is an important determinant of HIV infection by blood transfusion.

Correlation of CD8 Lymphocyte Activation with Cellular Viremia and Plasma HIV RNA Levels in Asymptomatic Patients Infected by Human Immunodeficiency Virus Type 1

Abstract: The relationship between CD8 lymphocyte phenotypic alterations and virological parameters was studied in 47 asymptomatic subjects with human immunodeficiency virus type 1 (HIV-1) infection and CD4 T cell counts above 400/μl. CD8 subsets were examined by means of three-color flow cytometry, using an extensive panel of monoclonal antibody combinations. Virological parameters were measured by both end-point dilution culture of peripheral blood mononuclear cells (PBMCs) and plasma and branched-DNA (bDNA) signal amplification of plasma HIV RNA. Whereas HIV-infected patients had a near-normal CD4 cell count (mean, 782 cells/μl), several subsets of activated CD8 cells were markedly expanded relative to values in 23 HIV-seronegative controls. The PBMC cultures were positive in 38 cases and plasma HIV RNA was detected in 31. The percentage of CD4 cells correlated negatively with both cellular viremia and plasma HIV RNA levels. Conversely, a positive correlation was observed between viral load and the perc...

Utility of SHIV for testing HIV-1 vaccine candidates in macaques.

Abstract: SUMMARY Intravenous injection of SHIV (simian/human immunodeficiency virus, chimeric virus) into rhesus macaques resulted in a viremia in peripheral blood lymphocytes (PBL) and the generation of anti-HIV-1 (human immunodeficiency virus type 1) envelope immune responses. A challenge stock of a SHIV containing HIV-1 HXBc2 envelope glycoproteins was prepared from infected rhesus monkey peripheral blood mononuclear cells (PBMC). The minimum animal infectious dose of the SHIV stock was determined and used in a challenge experiment to test protection. The vaccination of two rhesus monkeys with whole inactivated HIV-1 plus polydicarboxylatophenoxy phosphazene (PCPP) as the adjuvant protected the animals from becoming infected by a SHIV challenge. This experiment demonstrated for the first time that monkeys immunized with HIV-1 antigens can be protected against an HIV-1 envelope-containing virus. As the challenge virus was prepared from monkey PBMC, human antigens were unlikely to be involved in the protection. Protection of rhesus monkeys from SHIV challenge may help,define protective immune responses stimulated by HIV-1 vaccine candidates.

Monitoring of CMV infection: a comparison of PCR from whole blood, plasma-PCR, pp65-antigenemia and virus culture in patients after bone marrow transplantation.

Abstract: Rapid, specific and sensitive methods are essential for early detection of CMV infection in patients after marrow transplantation. Thus, in a prospective study, PCR from whole blood, plasma-PCR, pp65-antigenemia and virus culture were used and compared in 20 consecutive marrow transplant recipients for early diagnosis of CMV infection and monitoring of antiviral therapy. Moreover, semi-quantification of the viral load in blood samples by PCR from whole blood or plasma and pp65-antigenemia was performed. Fifteen out of 20 patients were found to be CMV positive by PCR from whole blood, plasma-PCR and pp65-antigenemia, whereas only 9/20 developed culture-proven viremia and/or viruria. PCR from whole blood, plasma-PCR and pp65-anti-genemia revealed identical results in 96 and discordant results in 13 of 109 blood samples (P < 0.01). The efficacy of antiviral therapy was monitored by semi-quantitative scoring of pp65-antigen-positive leukocytes and/or CMV-DNA levels in blood and plasma samples. Twelve of 13 patients were found to be CMV negative by all methods after 14 days of ganciclovir therapy. A good correlation of the semi-quantitative evaluation of the three assays was demonstrated. Thus, all three highly sensitive assays seem to be suitable for screening patients at risk for CMV infection and monitoring the efficacy of antiviral therapy.

Kinetics of appearance of neutralizing antibodies in 12 patients with primary or recent HIV-1 infection and relationship with plasma and cellular viral loads.

Abstract: HIV-1 primary infection is characterized by a short high titer viremia, which rapidly declines as the immune response emerges. The role of autologous neutralizing antibodies in the decline of viral replication was evaluated in 12 patients with primary or recent HIV-1 infection. Neutralizing antibodies detected for each patient could not generally be observed before several months after isolation of the first obtained HIV isolate. The plasma viral load, as measured by quantitation of the HIV-1 RNA, underwent a global decrease during the first 6 months of the infection, but this decrease did not seem to be associated with the emergence of neutralizing antibodies. The proviral load in peripheral blood mononuclear cells, which was studied by quantitative DNA polymerase chain reaction, exhibited fluctuations and was not as well curtailed as the plasma viremia in the majority of patients.

Intrarectal transmission of simian immunodeficiency virus in rhesus macaques: selective amplification and host responses to transient or persistent viremia.

Abstract: Intrarectal simian immunodeficiency virus (SIV) infection in rhesus macaques is a model for sexual transmission of primate retroviruses. Phylogenetic studies on envelope gene sequences that were present in blood following intrarectal SIV inoculation provided evidence for selective amplification of a subset of viruses present in the inoculum and defined one amino acid sequence uniquely associated with intrarectal infection. Both persistent and transient viremia states were observed after intrarectal infection. Immune responses in persistently infected animals accounted for slower rates of disease progression despite the presence of highly pathogenic viruses that were documented by transfusion studies. Transient viremia elicited protective immunity against subsequent intrarectal virus challenge but did not protect against intravenous virus challenge. Transient viremia usually but not always led to self-limiting infection. In one animal, we documented a relapse to active viremia long after the initial transient viremia. SIV transmission across mucosal barriers affects pathogenesis in the short term by limiting the types of viruses established in the host and in the longer term by establishing host responses that slow disease progression despite the presence of highly pathogenic viruses in blood.

Dynamics of HIV-1 replication following influenza vaccination of HIV+ individuals.

Abstract: Levels of HIV-1 have been reported to increase in peripheral blood after influenza vaccination of HIV+ individuals. In this study we have evaluated the dynamics of these changes. Ten HIV-1+ individuals classified in revised CDC clinical categories B and C as well as five seronegative healthy controls were vaccinated with the recommended influenza strains. HIV viral RNA and proviral DNA were sequentially quantified in serum and blood lymphocytes, respectively. Nine of the 10 HIV+ individuals had an increase in the frequency of infected CD4 cells 2 weeks after influenza vaccination. Individuals with low viral load had a rapid increase in viraemia and a small increase in frequency of infected cells in peripheral blood. In contrast, individuals with high viral load had a small drop in viraemia followed by a significant rise in the rate of infected cells. The observed changes may resemble those taking place during intercurrent infections in HIV+ individuals. The effects of the relative increases in infectious virus after the transient viraemic phase should be further investigated to evaluate potential risks of vaccination.

Feline immunodeficiency virus vaccination: characterization of the immune correlates of protection.

Abstract: Whole inactivated virus (WIV) vaccines derived from the FL4 cell line protect cats against challenge with feline immunodeficiency virus (FIV). To investigate the correlates of protective immunity induced by WIV, we established an immunization regimen which protected a proportion of the vaccinates against challenge. A strong correlation was observed between high virus neutralizing antibody titers and protection following challenge. To investigate further the immune mechanisms responsible for immunity, all of the vaccinates were rechallenged 35 weeks following the initial challenge. Results of virus isolation from peripheral blood mononuclear cells indicated that 9 of 10 vaccinates were protected from viremia following the second challenge, suggesting that vaccine-induced immunity to FIV persisted for at least 8 months. However, more stringent analysis for evidence of infection revealed that 5 of 10 vaccinates harbored virus in lymphoid tissues. Unlike the protection observed immediately following vaccination, which correlated positively with virus neutralizing antibody titer, the ability to resist a second challenge with FIV was more closely correlated with the induction of Env-specific cytotoxic T-cell activity. The results indicate that both virus-specific humoral immunity and cellular immunity play a role in the protection induced in cats by WIV immunization but their relative importance may be dependent on the interval between vaccination and exposure to virus.