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A 14‐month‐old, female Javan silvered leaf monkey (Trachypithecus auratus auratus) was presented for inguinal circular, erythematous, crusty dermatitis. The animal was bright and alert, and appetite was good. Lesions progressed to the whole abdomen and became ulcerative. Skin biopsies revealed a cutaneous lymphoma and no metastases were detected on computed tomography scan. Anti‐tumoral treatment was attempted with masitinib (50 mg orally every 48 hours), a tyrosine kinase inhibitor. In the absence of improvement of the lesions, as treatment was well tolerated, masitinib dose was increased to 50 mg orally once a day. Effect on the lesions was minimal, clinical condition worsened and the animal died 9 months after initial presentation. Postmortem examination and histopathology confirmed multicentric epitheliotropic CD3+ cutaneous lymphoma. To the authors' knowledge, this is the first report of cutaneous lymphoma in a langur, and the first attempt of treatment with masitinib in a non‐human primate species. Despite poor response, masitinib treatment appeared safe. [ABSTRACT FROM AUTHOR]

Abstract The complete nucleotide sequences of three chimpanzee polyomavirus genetic variants were determined. Phylogenetic analysis indicated that the viruses form two different genotypes of ChPyV. Comparison with other primate polyomaviruses revealed a putative agnogene, and an unusually long VP1 open reading frame. The transcriptional control regions (TCR) of the viruses were extremely short (155 nucleotides), and highly conserved amongst the genotypes. Analysis of the TCR from different chimpanzee subspecies, and from a series of tissues from five individuals confirmed its genetic stability, and also indicates that double-infections with different genotypes can occur.

The brown lemur population (Eulemur fulvus spp.) in Mbouzi islet is not native, and was introduced in 1997. Since then, the population has grown. In 2012 the National Council for Protection of Nature of Mayotte requested to remove this population of lemurs from Mbouzi, as they were suspected to be a threat to the protected endemic flora of the islet. The Association Francophone des Vétérinaires de Parcs Zoologiques (French-speaking Zoo Veterinarians Association, AFVPZ) was asked to conduct a biomedical evaluation of the population. Fifty-two animals were captured, anesthetized, and weighed. They all underwent a general physical examination. Feces were sampled for bacterial and parasitological screening. Hair was sampled for genetic studies and blood was sampled for hematology, biochemistry, viral serology, and haemoparasitology. Results showed that three individuals had a positive feces culture for Salmonella enterica and six had Lemuricola or Callistoura parasite infestations. Blood analyses for hematology and biochemistry showed 46 animals with elevated transferrin, 42 with low ferritin levels, 19 with hyperglycemia, and 10 with neutrophilia. Finally, 10 were positive for Toxoplasma serology, one was positive for α herpesvirus, five for pox virus, five for simian virus 40, and two for flavivirus. This publication reports the first complete biomedical evaluation of lemurs on Mayotte Island. [ABSTRACT FROM AUTHOR]

Background: Primate T-lymphotropic viruses type 1 (PTLV-1) are complex retroviruses infecting both human (HTLV-1) and simian (STLV-1) hosts. They share common epidemiological, clinical and molecular features. In addition to the canonical gag, pol, env retroviral genes, PTLV-1 purportedly encodes regulatory (i.e. Tax, Rex, and HBZ) and accessory proteins (i.e. P12/8, P13, P30). The latter have been found essential for viral persistence in vivo. Methodology/Principal findings: We have isolated a STLV-1 virus from a bonnet macaque (Macaca radiata–Mra18C9), a monkey from India. The complete sequence was obtained and phylogenetic analyses were performed. The Mra18C9 strain is highly divergent from the known PTLV-1 strains. Intriguingly, the Mra18C9 lacks the 3 accessory open reading frames. In order to determine if the absence of accessory proteins is specific to this particular strain, a comprehensive analysis of the complete PTLV-1 genomes available in Genbank was performed and found that the lack of one or many accessory ORF is common among PTLV-1. Conclusion: This study raises many questions regarding the actual nature, role and importance of accessory proteins in the PTLV-1 biology. [ABSTRACT FROM AUTHOR]

A 27-year-old male chimpanzee ( Pan troglodytes verus) developed signs of thrombotic thrombocytopenic purpura ( TTP). ADAMTS13 deficiency appeared to be the cause of disease. After treatment with high-dose prednisone, haematological values and clinical signs recovered. This is the first description of spontaneous TTP associated with ADAMTS13 deficiency in a non-human primate. [ABSTRACT FROM AUTHOR]

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in ‘natural host’ species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections. [ABSTRACT FROM AUTHOR]

The mosquito-borne West Nile virus (WNV) causes human and animal disease with outbreaks in several parts of the world including North America, the Mediterranean countries, Central and East Europe, the Middle East, and Africa. Particularly in elderly people and individuals with an impaired immune system, infection with WNV can progress into a serious neuroinvasive disease. Currently, no treatment or vaccine is available to protect humans against infection or disease. The goal of this study was to develop a WNV-vaccine that is safe to use in these high-risk human target populations. We performed a vaccine efficacy study in non-human primates using the contemporary, pathogenic European WNV genotype 1a challenge strain, WNV-Ita09. Two vaccine strategies were evaluated in rhesus macaques (Macaca mulatta) using recombinant soluble WNV envelope (E) ectodomain adjuvanted with Matrix-M, either with or without DNA priming. The DNA priming immunization was performed with WNV-DermaVir nanoparticles. Both vaccination strategies successfully induced humoral and cellular immune responses that completely protected the macaques against the development of viremia. In addition, the vaccine was well tolerated by all animals. Overall, The WNV E protein adjuvanted with Matrix-M is a promising vaccine candidate for a non-infectious WNV vaccine for use in humans, including at-risk populations. [ABSTRACT FROM AUTHOR]

Great apes are extremely sensitive to infections with human respiratory viruses. In this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. More than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the human respiratory viruses RSV (respiratory syncytial virus, hMPV (human metapneumovirus), H1N1 and H3N2 influenza A viruses, and influenza B virus. In all ape species high seroprevalences were found for RSV, hMPV, and influenza B virus. A high percentage of captive chimpanzees also showed evidence of influenza A H1N1 infections, and had low levels of H3N2 antibodies, while in sera from gorillas and orang-utans antibody levels to influenza A and B viruses were much lower or practically absent. Transmission of respiratory viruses was examined in longitudinal sera of young chimpanzees, and in chimpanzee sera taken during health checks. In young animals isolated cases of influenza infections were monitored, but evidence was found for single introductions followed by a rapid dissemination of RSV and hMPV within the group. Implementation of strict guidelines for handling and housing of nonhuman primates was shown to be an efficient method to reduce the introduction of respiratory infections in colonies of captive animals. RSV seroprevalence rates of chimpanzees remained high, probably due to circulating virus in the chimpanzee colony. [ABSTRACT FROM AUTHOR]

The complete nucleotide sequences of three chimpanzee polyomavirus genetic variants were determined. Phylogenetic analysis indicated that the viruses form two different genotypes of ChPyV. Comparison with other primate polyomaviruses revealed a putative agnogene, and an unusually long VP1 open reading frame. The transcriptional control regions (TCR) of the viruses were extremely short (155 nucleotides), and highly conserved amongst the genotypes. Analysis of the TCR from different chimpanzee subspecies, and from a series of tissues from five individuals confirmed its genetic stability, and also indicates that double-infections with different genotypes can occur. [ABSTRACT FROM AUTHOR]

As in HIV-1 infection in humans, SIVsm infection of rhesus macaques causes a slow progressive loss of CD4 T-cells followed by the onset of AIDS. In addition, there is a loss of dendritic cells (DC) in peripheral blood, peripheral lymphoid tissues, and the skin. Increasing the number of CD4 T cells and DC may be an important step in restoring immune competence and thus delay disease progression. Recently, progenipoietins (ProGP), a new family of chimeric Flt3 and G-CSF receptor agonists, were demonstrated to possess the capacity to mobilize hematopoietic progenitor cells in normal rhesus monkeys. In addition, these molecules induced increased numbers of myeloid cells, including dendritic cells, in the blood. Here we demonstrate that SIVsm-infected macaques, treated with ProGP-1, developed increased numbers of both plasmacytoid (CD123+, CD11c-) and myeloid (both CD11b+, CD11c+, and CD123-, CD11c+ subsets) DC and CD4 and CD8 T cells in peripheral blood. Importantly, during treatment, no changes in plasma virus load were observed. After 14 to 20 days of treatment, antibodies were formed against ProGP in all animals. As a consequence, white blood cell levels returned to baseline in several animals. In other animals values only returned to baseline after termination of ProGP treatment. In conclusion, ProGP-1 may be used to generate a transient increase in DC as well as CD4 T-cell numbers, thereby creating a window of opportunity for immunotherapeutic intervention. [Copyright &y& Elsevier]

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans. [ABSTRACT FROM AUTHOR]

Primates are naturally infected with herpesviruses. During the last 15 years, the search for homologues of human herpesviruses in nonhuman primates allowed the identification of numerous viruses belonging to the different herpesvirus subfamilies and genera. No simian homologue of human herpesvirus 7 (HHV7) has been reported to date. To investigate the putative existence of HHV7-like viruses in African great apes, we applied the consensus-degenerate hybrid oligonucleotide primers (CODEHOP) program- mediated PCR strategy to blood DNA samples from the four common chimpanzee subspecies (Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii), pygmy chimpanzees (Pan paniscus), as well as lowland gorillas (Gorilla gorilla gorilla). This study led to the discovery of a novel roseolovirus close to HHV7 in each of these nonhuman primate species and subspecies. Generation of the partial glycoprotein B (1,111-bp) and full-length DNA polymerase (3,036/3,042-bp) gene sequences allowed the deciphering of their evolutionary relationships. Phylogenetic analyses revealed that HHV7 and its African great ape homologues formed well-supported monophyletic lineages whose topological resemblance to the host phylogeny is suggestive of virus-host codivergence. Notably, the evolutionary branching points that separate HHV7 from African great ape herpesvirus 7 are remarkably congruent with the dates of divergence of their hosts. Our study shows that African great apes are hosts of human herpesvirus homologues, including HHV7 homologues, and that the latter, like other DNA viruses that establish persistent infections, have cospeciated with their hosts. [ABSTRACT FROM AUTHOR]

Phylogenetic analysis of foamy virus sequences obtained from Bornean and Sumatran orangutans showed a distinct clustering pattern. One subcluster was represented by both Bornean and Sumatran orangutan simian foamy viruses (SFV). Combined analysis of host mitochondrial DNA and SFV phylogeny provided evidence for the hypothesis of the repopulation of Sumatra by orangutans from Borneo. [ABSTRACT FROM AUTHOR]

Evidence is accumulating that CD4+ T-helper (Th) responses play a critical role in facilitating effector responses which are capable of controlling and even preventing human immunodeficiency virus (HIV) infection. The present work was undertaken to determine whether immunization with multiple antigens influenced individual Th responses and increased protection relative to a single antigen. Rhesus macaques were primed with DNA and boosted (immune-stimulating complex-formulated protein) with a combination of regulatory and structural antigens (Tat-Env-Gag) or with Tat alone. Immunization with combined antigens reduced the magnitude of the responses to Tat compared to the single-antigen immunization. Interestingly, the Th immune responses to the individual antigens were noticeably different. To determine whether the qualitative differences in vaccine-induced Th responses correlated with vaccine efficacy, animals were challenged intravenously with simian/human immunodeficiency virus (strain SHIV89.6p) 2 months following the final immunization. Animals that developed combined Th1- and Th2-like responses to Gag and Th2 dominant Env-specific responses were protected from disease progression. Interestingly, one animal that was completely protected from infection had the strongest IFN-γ and interleukin-2 (IL-2) responses prior to challenge, in addition to very strong IL-4 responses to Gag and Env. In contrast, animals with only a marked vaccine-induced Tat-specific Th2 response (no IFN-γ) were not protected from infection or disease. These data support the rationale that effective HIV vaccine-induced immunity requires a combination of potent Th1- and Th2-like responses best directed to multiple antigens. [ABSTRACT FROM AUTHOR]

The full-length proviral genome of a foamy virus infecting a Bornean orangutan was amplified, and its sequence was analyzed. Although the genome showed a clear resemblance to other published foamy virus genomes from apes and monkeys, phylogenetic analysis revealed that simian foamy virus SFVora was evolutionarily equidistant from foamy viruses from other hominoids and from those from Old World monkeys. This finding suggests an independent evolution within its host over a long period of time. [ABSTRACT FROM AUTHOR]

Current data suggest that the human immunodeficiency virus type 1 (HIV-1) epidemic arose by transmission of simian immunodeficiency virus (SIV) SIVcpz from a subspecies of common chimpanzees (Pan troglodytes troglodytes) to humans. SIVcpz of chimpanzees is itself a molecular chimera of SIVs from two or more different monkey species, suggesting that recombination was made possible by coinfection of one individual animal with different lentiviruses. However, very little is known about SIVcpz transmission and the susceptibility to lentivirus coinfection of its natural host, the chimpanzee. Here, it is revealed that either infected plasma or peripheral blood mononuclear cells readily confer infection when exposure occurs by the intravenous or mucosal route. Importantly, the presence of preexisting HIV-1 infection did not modify the kinetics of SIVcpz infection once it was established by different routes. Although humoral responses appeared as early as 4 weeks postinfection, neutralization to SIVcpz-ANT varied markedly between animals. Analysis of the SIVcpz env sequence over time revealed the emergence of genetic viral variants and persistent SIVcpz RNA levels of between 104 and 105 copies/ml plasma regardless of the presence or absence of concurrent HIV-1 infection. These unique data provide important insight into possible routes of transmission, the kinetics of acute SIVcpz infection, and how readily coinfection with SIVcpz and other lentiviruses may be established as necessary preconditions for potential recombination. [ABSTRACT FROM AUTHOR]

In November 2021, seven western lowland gorillas and four Asiatic lions were diagnosed with COVID-19 at Rotterdam Zoo. An outbreak investigation was undertaken to determine the source and extent of the outbreak and to identify possible transmission routes. Interviews were conducted with staff to identify human and animal contacts and cases, compliance with personal protective equipment (PPE) and potential transmission routes. Human and animal contacts and other animal species suspected to be susceptible to SARS-CoV-2 were tested for SARS-CoV-2 RNA. Positive samples were subjected to sequencing. All the gorillas and lions that could be tested (3/7 and 2/4, respectively) were RT-PCR positive between 12 November and 10 December 2021. No other animal species were SARS-CoV-2 RNA positive. Forty direct and indirect human contacts were identified. Two direct contacts tested RT-PCR positive 10 days after the first COVID-19 symptoms in animals. The zookeepers' viral genome sequences clustered with those of gorillas and lions. Personal protective equipment compliance was suboptimal at instances. Findings confirm transmission of SARS-CoV-2 among animals and between humans and animals but source and directionality could not be established. Zookeepers were the most likely source and should have periodic PPE training. Sick animals should promptly be tested and isolated/quarantined.

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials., Competing Interests: Author EP was employed by Biofabri. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mooij, García-Arriaza, Pérez, Lázaro-Frías, Verstrepen, Böszörményi, Mortier, Fagrouch, Kiemenyi-Kayere, Niphuis, Acar, Meijer, Stammes, Kondova, Verschoor, GeurtsvanKessel, de Bruin, Sikkema, Luczkowiak, Delgado, Montenegro, Puentes, Rodríguez, Bogers, Koopman and Esteban.)

The brown lemur population ( Eulemur fulvus spp.) in Mbouzi islet is not native, and was introduced in 1997. Since then, the population has grown. In 2012 the National Council for Protection of Nature of Mayotte requested to remove this population of lemurs from Mbouzi, as they were suspected to be a threat to the protected endemic flora of the islet. The Association Francophone des Vétérinaires de Parcs Zoologiques (French-speaking Zoo Veterinarians Association, AFVPZ) was asked to conduct a biomedical evaluation of the population. Fifty-two animals were captured, anesthetized, and weighed. They all underwent a general physical examination. Feces were sampled for bacterial and parasitological screening. Hair was sampled for genetic studies and blood was sampled for hematology, biochemistry, viral serology, and haemoparasitology. Results showed that three individuals had a positive feces culture for Salmonella enterica and six had Lemuricola or Callistoura parasite infestations. Blood analyses for hematology and biochemistry showed 46 animals with elevated transferrin, 42 with low ferritin levels, 19 with hyperglycemia, and 10 with neutrophilia. Finally, 10 were positive for Toxoplasma serology, one was positive for α herpesvirus, five for pox virus, five for simian virus 40, and two for flavivirus. This publication reports the first complete biomedical evaluation of lemurs on Mayotte Island.

The incidence of simian virus 40 (SV40) infections in rhesus macaques infected with simian-human immunodeficiency viruses (SHIV) and in uninfected animals was determined using PCR. Rates varied from 5% in peripheral blood mononuclear cells of uninfected monkeys to 19.6% in SHIV-infected macaques. Much higher detection rates, up to 75%, were found in lymph nodes and spleen samples of SHIV-infected animals. Sequence analysis of PCR amplicons revealed that they form two genetic clusters, one containing the majority of known SV40 strains and the other formed by variants with 7% genetic difference. Based on this difference, we propose two SV40 types: "type 1" or "classical type" for the majority of SV40 strains and "type 2" for the novel SV40 variants. The genome of one variant, SV40-Ri257, was completely sequenced and analyzed. The agnogene of SV40-Ri257 extends into the VP2 open reading frame and encodes a typical agnoprotein fused to a C-terminal hydrophobic region. The transcriptional control region (TCR) of SV40-Ri257 is the least conserved region compared to type 1 viruses. Particularly, the 3' end of the TCR, containing the early promoter and enhancer region, exhibits considerable variation. Further analysis of SHIV-infected macaques with type-specific PCRs revealed that the TCR of type 1 was completely conserved, whereas this region in type 2 varied considerably within the early enhancer region. We provide evidence here for the existence of a novel SV40 type in rhesus macaques and show that double infections with both types frequently occur.

Serological screening of sera from orang-utans demonstrated a high percentage of sera that cross-reacted with antigens of the polyomavirus (PyV) simian virus 40. Analysis of archival DNA samples from 71 Bornean and eight Sumatran orang-utans with a broad-spectrum PCR assay resulted in the detection of PyV infections in 11 animals from both species. Sequence analysis of the amplicons revealed considerable differences between the PyVs from Bornean and Sumatran orang-utans. The genome from two PyVs, one from each species, was therefore amplified and sequenced. Both viral genomes revealed a characteristic PyV architecture, but lacked an obvious agnogene. Neighbour-joining analysis positioned the viruses in a large cluster together with viruses from bats, bovines, rodents and several primate PyVs from chimpanzees, African green monkeys, squirrel monkeys and the human Merkel cell PyV.

Old age is accompanied by an increased incidence of infection and poorer responses to vaccination. In this proof of principle study, old female rhesus macaques (aged 18.5 to 23.9 years) were treated with recombinant simian interleukin-7 (IL-7) or saline, according to a two-phase regime. Treatment was not associated with bone loss as judged by plasma carboxy terminal telopeptide of type I collagen (ICTP) levels, nor with neutropenia. IL-7-treated animals showed an increase in the number of blood CD4(+) CD3(+) and CD8(+) CD3(+) T cells after both phases of treatment and a transient increase in the number of naïve (CD62L(+) CD45RA(+)) T cells for both CD4(+) and CD8(+) subsets after only the first treatment. Increases in TREC levels per T cell followed both phases of treatment, but were more prolonged after the second phase. Following vaccination with inactivated influenza strain A/PR/8/34, hemagglutination inhibition assays showed that half of the IL-7-treated animals showed a greater than eight-fold increase in antibody titer following the first challenge with the vaccine. In addition IL-7-treated animals showed higher numbers of central memory CD8(+) T cells compared to pretreatment levels with numbers greater than in the saline-treated group. Animals with the highest hemagglutination inhibition titers and the best proliferation against flu antigen were among those with the highest TREC per T cell levels after the second phase of treatment. Treatment of the elderly with IL-7 may provide an effective therapy to improve the immune system.

Accumulating evidence suggests that exposed individuals may acquire multiple human immunodeficiency virus (HIV) infections more frequently than originally believed. As a result, circulating recombinant forms of HIV are emerging that are of particular concern in the AIDS epidemic and HIV vaccine development efforts. The aim of this study was to determine under what conditions secondary or superinfections of HIV or simian immunodeficiency virus (SIV) may be acquired under controlled settings in well-defined, non-human primate models. Retrospective analysis of macaques that had acquired apparent immunity upon infection with a defined attenuated SIV(mac) strain revealed that eight out of eight animals that were secondarily exposed to a new virus variant became infected with the new virus strain, but at low levels. Interestingly, similarly high frequencies of secondary infections were observed after early (4 months), as well as late (5 years), exposure following primary infection. As possible causes of susceptibility to secondary infections, perturbations in the immune system associated with exacerbated infections were then investigated prospectively. Results revealed that short-term immune-suppression therapy did not increase susceptibility to secondary infections. Taken together, data suggested that neither early- nor late-exposure immune-suppressive events following primary infection accounted for the observed high incidence of secondary infections. With HIV-1, the question of whether secondary infections with very closely related viral variants could occur in the chimpanzee model was addressed. In both animal models, secondary infections were confirmed, notably with relatively closely related SIV(mac) or HIV-1 strains, following a single exposure to the secondary virus strain. These findings reveal that secondary lentiviral infections may be acquired readily during different stages of primary infection, in contrast to co-infections, which are acquired at the moment of initial infection.

Candidate human immunodeficiency virus (HIV) vaccine strategies that induce strong cellular immune responses protect rhesus macaques that are infected with recombinant simian/human immunodeficiency virus SHIV89.6p from acute CD4+ T-cell loss and delay progression to AIDS. However, similar strategies have not proven as efficacious in the simian immunodeficiency virus (SIV)mac model of AIDS, an infection that causes a slow, steady loss of CD4+ T-cell function and numbers in rhesus macaques similar to that caused by HIV-1, the principal cause of AIDS in humans. Efforts to increase vaccine efficacy by repeated boosting with the same vector are quickly limited by rising anti-vector immune responses. Here, the sequential use of three different vectors (DNA, Semliki Forest virus and modified vaccinia virus Ankara) encoding the same SIVmac structural and regulatory antigens was investigated and demonstrated to prevent or slow the loss of CD4+ T-cells after mucosal challenge with the highly pathogenic SIVmac251 strain. Of particular interest was an inverse association between the extent of T-helper 2 cytokine responses and steady-state virus load. Although limited in the number of animals, this study provides important proof of the efficacy of the triple-vector vaccine strategy against chronic, progressive CD4+ T-cell loss in the rigorous SIVmac/rhesus macaque model of AIDS.

A novel simian immunodeficiency virus (SIV) was characterized from a Schmidt's guenon (Cercopithecus ascanius schmidti), which was housed in a local zoo. The virus infection was detected during a routine serological screening for antibodies that were cross-reactive with SIVmac antigens. Infection with an immunodeficiency virus was confirmed using an INNO-LIA HIV Confirmation assay. Using DNA isolated from a blot clot, a 1895 nt partial pol sequence was amplified and sequenced. Phylogenetic analysis showed that this virus, designated SIVschm, shares a distant relationship with SIVgsn, isolated from greater spot-nosed monkeys, and is one of the most divergent SIVs identified to date.

To determine whether passage of late-stage variants of simian immunodeficiency virus (SIV) would lead to a more virulent infection and rapid disease progression, a study was designed to examine the effects of selective transmission of SIV from late-stage cases of AIDS in Macaca mulatta. In a uniform group of 10 age-matched animals from the same genetic breeding stock infected with SIV(B670), it took 7 months before one of the ten animals developed AIDS. Passage of virus taken from this animal immediately prior to death resulted in death of the recipient due to AIDS within 4 months. Again, subsequent passage of virus taken late in disease resulted in an accelerated disease course, with AIDS developing within 2.5 and 1.8 months in two recipients. The fourth passage of virus taken late in disease from the most rapid progressor (1.8 months) resulted in AIDS developing in this recipient within 1 month of infection. During each consecutive passage in vivo, the loss of memory T cells became more acute. Evidence that the virus became more virulent with selective passage of late-stage variants was provided by the markedly increased levels of both plasma antigen and viral RNA. Subsequent in vivo passage from end-stage AIDS selected for a strain of SIV capable of causing the acute development of AIDS as rapidly as 1 month post-infection. The pathology of acute AIDS in these cases closely resembled that seen after a chronic disease course.