Murray Gardner - Academia.edu (original) (raw)

Papers by Murray Gardner

Research paper thumbnail of Evolution of compatible replicons of the related IncQ-like plasmids, pTC-F14 and pTF-FC2

Microbiology (Reading, England), 2004

Two closely related but compatible plasmids of the IncQ-2alpha and IncQ-2beta groups, pTF-FC2 and... more Two closely related but compatible plasmids of the IncQ-2alpha and IncQ-2beta groups, pTF-FC2 and pTC-F14, were discovered in two acidiphilic chemolithotrophic bacteria. Cross-complementation and cross-regulation experiments by the replication proteins were carried out to discover what changes were necessary when the plasmids evolved to produce two incompatibility groups. The requirement of a pTC-F14 oriV for a RepC DNA-binding protein was plasmid specific, whereas the requirement for the RepA helicase and RepB primase was less specific and could be complemented by the IncQ-2alpha plasmid pTC-FC2, and the IncQ-1beta plasmid pIE1108. None of the IncQ-1alpha plasmid replication proteins could complement the pTC-F14 oriV, and pTC-F14 and RSF1010 were incompatible. This incompatibility was associated with the RepC replication protein and was not due to iteron incompatibility. Replication of pTC-F14 took place from a 5.7 kb transcript that originated upstream of the mobB gene located wit...

Research paper thumbnail of Isolation of a New Broad-Host-Range IncQ-Like Plasmid, pTC-F14, from the Acidophilic Bacterium Acidithiobacillus caldus and Analysis of the Plasmid Replicon

Journal of Bacteriology, 2001

A moderately thermophilic (45 to 50°C), highly acidophilic (pH 1.5 to 2.5), chemolithotrophic Aci... more A moderately thermophilic (45 to 50°C), highly acidophilic (pH 1.5 to 2.5), chemolithotrophic Acidithiobacillus caldus strain, f, was isolated from a biooxidation process used to treat nickel ore. Trans-alternating field electrophoresis analysis of total DNA from the A. caldus cells revealed two plasmids of approximately 14 and 45 kb. The 14-kb plasmid, designated pTC-F14, was cloned and shown by replacement of the cloning vector with a kanamycin resistance gene to be capable of autonomous replication in Escherichia coli . Autonomous replication was also demonstrated in Pseudomonas putida and Agrobacterium tumefaciens LBA 4404, which suggested that pTC-F14 is a broad-host-range plasmid. Sequence analysis of the pTC-F14 replicon region revealed five open reading frames and a replicon organization like that of the broad-host-range IncQ plasmids. Three of the open reading frames encoded replication proteins which were most closely related to those of IncQ-like plasmid pTF-FC2 (amino ac...

Research paper thumbnail of Assay for type C virus in mouse sera based on particulate reverse transcriptase activity

Journal of Virology, 1976

Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infecte... more Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infected with type C virus provides a sensitive and rapid procedure for the determination of in vivo virus infection. The results compare well with assays for infectious virus and with complement fixation or competitive radio-immunoassays for the p30 internal antigen of the virus.

Research paper thumbnail of Induction of Disseminated Virulent Cytomegalovirus Infection by Immunosuppression of Naturally Chronically Infected Wild Mice

Infection and Immunity, 1974

Wild mice immunosuppressed with antithymocytic sera show a high incidence of disseminated virulen... more Wild mice immunosuppressed with antithymocytic sera show a high incidence of disseminated virulent cytomegalovirus infection.

Research paper thumbnail of Immune response of rhesus macaques to recombinant simian immunodeficiency virus gp130 does not protect from challenge infection

Journal of Virology, 1993

Simian immunodeficiency virus (SIV) infection of rhesus macaques is a model for human immunodefic... more Simian immunodeficiency virus (SIV) infection of rhesus macaques is a model for human immunodeficiency virus (HIV) infection in humans. Inactivated and modified live whole-virus vaccines have provided limited protective immunity against SIV in rhesus macaques. Because of safety concerns in the use of inactivated and live whole-virus vaccines, we evaluated the protective immunity of vaccinia virus recombinants expressing the surface glycoprotein (gp130) of SIVmac and subunit preparations of gp130 expressed in mammalian cells (CHO). Three groups of animals were immunized with recombinant SIV gp130. The first group received SIV gp130 purified from genetically engineered CHO cells (cSIVgp130), the second group was vaccinated with recombinant vaccinia virus expressing SIVmac gp130 (vSIVgp130), and the third group was first primed with vSIVgp130 and then given a booster immunization with cSIVgp130. Although anti-gp130 binding antibodies were elicited in all three groups, neutralizing anti...

Research paper thumbnail of Characterization of genome structure of amphotropic and ecotropic wild mouse retroviruses

Journal of Virology, 1982

We studied the RNA genomes of several wild mouse type C retroviruses by using RNase T1-oligonucle... more We studied the RNA genomes of several wild mouse type C retroviruses by using RNase T1-oligonucleotide fingerprinting. The amphotropic and ecotropic viruses of field strain 1504 produced very similar oligonucleotide fingerprints, but each also had several unique oligonucleotides. All of these unique oligonucleotides were located in the env gene region and were probably responsible for the host range differences between these viruses, as well as the lymphomagenic and paralytogenic properties of the viruses. We obtained similar results with the amphotropic and ecotropic viruses of another field strain (4070), which was isolated from a mouse from a different trapping area. The amphotropic viruses of several field strains (strains 1504, 4070, and 1313) were more closely related than the ecotropic viruses of different strains (strains 1504, 4070, and 4996). These findings suggested that the genetic sequences of the amphotropic viruses are more conserved than those of ecotropic viruses is...

Research paper thumbnail of Murine retroviral restriction genes Fv-4 and Akvr-1 are alleles of a single locus

Journal of Virology, 1983

The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, ... more The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, distributions, ranges of action, and phenotypes. Akvr-1 has been shown to segregate independently in backcrosses with a variety of retroviral restriction loci, including Fv-1, Fv-2, Ril-1, and Ril-2. An allelism test cross of FRG (Fv-4R) X LCRR (Akvr-1R) hybrids mated to AKR mice failed to produce any viremic offspring. These results suggested that Akvr-1R and Fv-4R are alleles of a single locus, Fv-4, on mouse chromosome 12.

Research paper thumbnail of Amphotropic host range of naturally occuring wild mouse leukemia viruses

Journal of Virology, 1976

Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely... more Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely separated areas in southern California show an unusually wide in vitro host range. They replicate well in human, feline, canine, guinea pig, rabbit, rat, and mouse cells, whereas bovine, hamster, and avian cells are resistant. Since this host range includes that of both mouse tropic (ecotropic) and xenotropic murine leukemia viruses, they are designated as "amphotropic". No purely xenotropic virus component is detectable in these field isolates. They may represent the "wild" or ancestral viruses from which the ecotropic and xenotrophic murine leukemia virus strains of laboratory mice have been derived.

Research paper thumbnail of Type C Virus Expression in Lymphoma-Paralysis-Prone Wild Mice2

JNCI: Journal of the National Cancer Institute, 1976

Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infec... more Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice.

Research paper thumbnail of A Spontaneous Lower Motor Neuron Disease Apparently Caused by Indigenous Type-C RNA Virus in Wild Mice2

JNCI: Journal of the National Cancer Institute, 1973

A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus m... more A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus musculus) which had a high incidence of naturally occurring lymphoma and elevated indigenous type-C virus activity. Experimental transmission evidence indicated that both the neurologic and lymphomatous disorders almost certainly were caused by the indigenous type-C virus. The virus appeared to have a direct neurotropic effect on anterior horn neurons in the lower spinal cord.

Research paper thumbnail of The epidemiology and virology of C-type virus-associated hematological cancers and related diseases in wild mice

Cancer research, 1976

In several different populations of wild mice, observed over a 35-month period in laboratory geri... more In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies.

Research paper thumbnail of Dietary fat affects immune response, production of antiviral factors, and immune complex disease in NZB/NZW mice

Proceedings of the National Academy of Sciences, 1982

Autoimmune-prone (NZB x NZW)F1 (B/W) mice fed three nearly isocaloric diets with varied fat conte... more Autoimmune-prone (NZB x NZW)F1 (B/W) mice fed three nearly isocaloric diets with varied fat content showed a marked difference in their spontaneous development of immune complex disease and their immune response. Those animals received the diets high in either unsaturated or saturated fats had more severe immune complex nephritis and died earlier than mice on the low-fat diet. Endogenous production of the mouse xenotropic virus was unaffected by dietary fats, but the serum lipoproteins associated with antiviral activity were increased to levels as high as 1:600,000 in the B/W mice on the high-fat diets. These lipoproteins may be partially responsible for the decreased mitogenic response of spleen cells from mice fed the two high-fat diets. The mice receiving a diet high in saturated fats produced substantially higher titers of natural thymocytotoxic autoantibody, an IgM class of antibody, than did the mice maintained either on the high-unsaturated-fat or low-fat diet. In contrast, t...

Research paper thumbnail of Induction of Simian AIDS in Infant Rhesus Macaques Infected with CCR5- or CXCR4-Utilizing Simian-Human Immunodeficiency Viruses Is Associated with Distinct Lesions of the Thymus

Journal of Virology, 2004

ABSTRACTNewborn rhesus macaques were infected with two chimeric simian-human immunodeficiency vir... more ABSTRACTNewborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1)envgenes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIVSF162P3or the CXCR4-utilizing SHIVSF33Aresulted in clinical manifestations consistent with simian AIDS. Most prominent in this study was the detection of severe thymic involution in all SHIVSF33A-infected infants, which is very similar to HIV-1-induced thymic dysfunction in children who exhibit a rapid pattern of disease progression. In contrast, SHIVSF162P3induced only a minor disruption in thymic morphology. Consistent with the distribution of the coreceptors CXCR4 and CCR5 within the thymus, the expression of SHIVSF162P3was restricted to the thymic medulla, whereas SHIVSF33Awas preferentially detected in the cortex. This dichotomy of tissue tropism is similar to the differential tropism of HIV-1 isolates observed in the...

Research paper thumbnail of Akvr-1, a dominant murine leukemia virus restriction gene, is polymorphic in leukemia-prone wild mice

Proceedings of the National Academy of Sciences, 1980

We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two al... more We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two alleles, Akvr-1R (restrictive) and Akvr-1r (susceptible), in a feral population of mice (Mus) musculus domesticus) at a squab farm near Lake Casitas (LC) in southern California. Akvr-1k is a dominant allele that exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-mediated lymphoma in LC (Akvr-1RR) X AKR F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in backcrosses to AKR mice. Akvr-1R likewise is effective in restriction of NB-tropic Moloney murine leukemia virus-induced viremia and NB-tropic Friend virus-induced splenomegaly but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three ecotropic viruses are similar to each other and distinct ...

Research paper thumbnail of Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

Journal of Virology, May 1, 1990

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-ligh... more Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenge exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

Research paper thumbnail of HTLV-III Antibody Screening of Blood Bank Donors

Research paper thumbnail of Experimental vaccine protection against homologous and heterologous strains of feline immunodeficiency virus

Journal of Virology, 1993

More than 90% of cats immunized with inactivated whole infected-cell or cell-free feline immunode... more More than 90% of cats immunized with inactivated whole infected-cell or cell-free feline immunodeficiency virus (FIV) vaccines were protected against intraperitoneal infection with 10 50% animal infectious doses of either homologous FIV Petaluma (28 of 30 cats) or heterologous FIV Dixon strain (27 of 28 cats). All 15 control cats were readily infected with either strain of FIV. Protection appears to correlate with antiviral envelope antibody levels by a mechanism yet to be determined.

Research paper thumbnail of Simian Retroviruses

AIDS and Other Manifestations of HIV Infection, 2004

Animal retroviruses are classified within seven different genera, of which members of five genera... more Animal retroviruses are classified within seven different genera, of which members of five genera are present in primates C-type virus, D-type virus, human T-cell leukemia virus (HTLV), simian T-cell lymphotropic virus (STLV), bovine leukemia virus (BLV), lentiviruses, and spuma or foamy viruses. This chapter reviews the salient biology of each of these five viral groups. Emphasis is placed on the D-type simian retroviruses (SRVs) and lentiviruses (SIVs) because of their etiologic association with simian AIDS (SAIDS). Humans also harbor retroviruses: two strains of human T-lymphotropic virus (HTLV-1 and HTLV-2) with simian counterparts (STLV-1 and STLV-2) and two major strains of lentivirus, human immunodeficiency virus (HIV-1 and HIV-2), which also have simian counterparts (SIVs). In the natural African simian hosts, SIV does not cause any disease, but experimental infection of captive macaques with certain SIV strains, especially from the sooty mangabey, produces a progressive and fatal immunodeficiency syndrome similar to AIDS in humans, making this primate lentivirus model very useful for research into AIDS pathogenesis, vaccines, and antiviral therapy.

Research paper thumbnail of Rhesus Macaques Inoculated With Molecularly Cloned Simian Immunodeficiency Virus

Journal of Medical Primatology, Jun 1, 1989

We have isolated a biologically active molecular clone of simian immunodeficiency virus (SIV), SI... more We have isolated a biologically active molecular clone of simian immunodeficiency virus (SIV), SIVmac 1A11, originally obtained from a rhesus macaque at the New England Regional Primate Research Center. Virus derived from cells transfected with this clone is cytopathic for rhesus peripheral blood mononuclear cells, replicates in cultures of rhesus macrophages, and infects rhesus macaques when inoculated intravenously. Six macaques inoculated with SIVmac 1A11 all became infected and produced antibodies to viral envelope glycoproteins that neutralized virus. Antibodies to viral core proteins were detected in only one animal. No clinical signs of disease were observed throughout 7 months postinoculation.

Research paper thumbnail of Development of a mouse mammary tumor virus-negative mouse strain: a new system for the study of mammary carcinogenesis

Journal of Virology, 1982

All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA in... more All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA integrated as proviral sequences. This complicates efforts to define viral-induced mammary carcinogenesis. Here we report the use of surgical nonlethal splenectomy in tissue typing mice and the development of an MMTV-negative mouse strain. The MMTV-negative strain allows study of the involvement of non-MMTV genes in mammary carcinogenesis. In addition, it can be used as a sterile background into which MMTV variants can be introduced. Through the techniques described here, mice containing single MMTV loci or specific combinations can be specially chosen and rapidly developed. In this manner, the oncogenecity of particular MMTV variants may be assessed.

Research paper thumbnail of Evolution of compatible replicons of the related IncQ-like plasmids, pTC-F14 and pTF-FC2

Microbiology (Reading, England), 2004

Two closely related but compatible plasmids of the IncQ-2alpha and IncQ-2beta groups, pTF-FC2 and... more Two closely related but compatible plasmids of the IncQ-2alpha and IncQ-2beta groups, pTF-FC2 and pTC-F14, were discovered in two acidiphilic chemolithotrophic bacteria. Cross-complementation and cross-regulation experiments by the replication proteins were carried out to discover what changes were necessary when the plasmids evolved to produce two incompatibility groups. The requirement of a pTC-F14 oriV for a RepC DNA-binding protein was plasmid specific, whereas the requirement for the RepA helicase and RepB primase was less specific and could be complemented by the IncQ-2alpha plasmid pTC-FC2, and the IncQ-1beta plasmid pIE1108. None of the IncQ-1alpha plasmid replication proteins could complement the pTC-F14 oriV, and pTC-F14 and RSF1010 were incompatible. This incompatibility was associated with the RepC replication protein and was not due to iteron incompatibility. Replication of pTC-F14 took place from a 5.7 kb transcript that originated upstream of the mobB gene located wit...

Research paper thumbnail of Isolation of a New Broad-Host-Range IncQ-Like Plasmid, pTC-F14, from the Acidophilic Bacterium Acidithiobacillus caldus and Analysis of the Plasmid Replicon

Journal of Bacteriology, 2001

A moderately thermophilic (45 to 50°C), highly acidophilic (pH 1.5 to 2.5), chemolithotrophic Aci... more A moderately thermophilic (45 to 50°C), highly acidophilic (pH 1.5 to 2.5), chemolithotrophic Acidithiobacillus caldus strain, f, was isolated from a biooxidation process used to treat nickel ore. Trans-alternating field electrophoresis analysis of total DNA from the A. caldus cells revealed two plasmids of approximately 14 and 45 kb. The 14-kb plasmid, designated pTC-F14, was cloned and shown by replacement of the cloning vector with a kanamycin resistance gene to be capable of autonomous replication in Escherichia coli . Autonomous replication was also demonstrated in Pseudomonas putida and Agrobacterium tumefaciens LBA 4404, which suggested that pTC-F14 is a broad-host-range plasmid. Sequence analysis of the pTC-F14 replicon region revealed five open reading frames and a replicon organization like that of the broad-host-range IncQ plasmids. Three of the open reading frames encoded replication proteins which were most closely related to those of IncQ-like plasmid pTF-FC2 (amino ac...

Research paper thumbnail of Assay for type C virus in mouse sera based on particulate reverse transcriptase activity

Journal of Virology, 1976

Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infecte... more Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infected with type C virus provides a sensitive and rapid procedure for the determination of in vivo virus infection. The results compare well with assays for infectious virus and with complement fixation or competitive radio-immunoassays for the p30 internal antigen of the virus.

Research paper thumbnail of Induction of Disseminated Virulent Cytomegalovirus Infection by Immunosuppression of Naturally Chronically Infected Wild Mice

Infection and Immunity, 1974

Wild mice immunosuppressed with antithymocytic sera show a high incidence of disseminated virulen... more Wild mice immunosuppressed with antithymocytic sera show a high incidence of disseminated virulent cytomegalovirus infection.

Research paper thumbnail of Immune response of rhesus macaques to recombinant simian immunodeficiency virus gp130 does not protect from challenge infection

Journal of Virology, 1993

Simian immunodeficiency virus (SIV) infection of rhesus macaques is a model for human immunodefic... more Simian immunodeficiency virus (SIV) infection of rhesus macaques is a model for human immunodeficiency virus (HIV) infection in humans. Inactivated and modified live whole-virus vaccines have provided limited protective immunity against SIV in rhesus macaques. Because of safety concerns in the use of inactivated and live whole-virus vaccines, we evaluated the protective immunity of vaccinia virus recombinants expressing the surface glycoprotein (gp130) of SIVmac and subunit preparations of gp130 expressed in mammalian cells (CHO). Three groups of animals were immunized with recombinant SIV gp130. The first group received SIV gp130 purified from genetically engineered CHO cells (cSIVgp130), the second group was vaccinated with recombinant vaccinia virus expressing SIVmac gp130 (vSIVgp130), and the third group was first primed with vSIVgp130 and then given a booster immunization with cSIVgp130. Although anti-gp130 binding antibodies were elicited in all three groups, neutralizing anti...

Research paper thumbnail of Characterization of genome structure of amphotropic and ecotropic wild mouse retroviruses

Journal of Virology, 1982

We studied the RNA genomes of several wild mouse type C retroviruses by using RNase T1-oligonucle... more We studied the RNA genomes of several wild mouse type C retroviruses by using RNase T1-oligonucleotide fingerprinting. The amphotropic and ecotropic viruses of field strain 1504 produced very similar oligonucleotide fingerprints, but each also had several unique oligonucleotides. All of these unique oligonucleotides were located in the env gene region and were probably responsible for the host range differences between these viruses, as well as the lymphomagenic and paralytogenic properties of the viruses. We obtained similar results with the amphotropic and ecotropic viruses of another field strain (4070), which was isolated from a mouse from a different trapping area. The amphotropic viruses of several field strains (strains 1504, 4070, and 1313) were more closely related than the ecotropic viruses of different strains (strains 1504, 4070, and 4996). These findings suggested that the genetic sequences of the amphotropic viruses are more conserved than those of ecotropic viruses is...

Research paper thumbnail of Murine retroviral restriction genes Fv-4 and Akvr-1 are alleles of a single locus

Journal of Virology, 1983

The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, ... more The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, distributions, ranges of action, and phenotypes. Akvr-1 has been shown to segregate independently in backcrosses with a variety of retroviral restriction loci, including Fv-1, Fv-2, Ril-1, and Ril-2. An allelism test cross of FRG (Fv-4R) X LCRR (Akvr-1R) hybrids mated to AKR mice failed to produce any viremic offspring. These results suggested that Akvr-1R and Fv-4R are alleles of a single locus, Fv-4, on mouse chromosome 12.

Research paper thumbnail of Amphotropic host range of naturally occuring wild mouse leukemia viruses

Journal of Virology, 1976

Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely... more Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely separated areas in southern California show an unusually wide in vitro host range. They replicate well in human, feline, canine, guinea pig, rabbit, rat, and mouse cells, whereas bovine, hamster, and avian cells are resistant. Since this host range includes that of both mouse tropic (ecotropic) and xenotropic murine leukemia viruses, they are designated as "amphotropic". No purely xenotropic virus component is detectable in these field isolates. They may represent the "wild" or ancestral viruses from which the ecotropic and xenotrophic murine leukemia virus strains of laboratory mice have been derived.

Research paper thumbnail of Type C Virus Expression in Lymphoma-Paralysis-Prone Wild Mice2

JNCI: Journal of the National Cancer Institute, 1976

Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infec... more Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice.

Research paper thumbnail of A Spontaneous Lower Motor Neuron Disease Apparently Caused by Indigenous Type-C RNA Virus in Wild Mice2

JNCI: Journal of the National Cancer Institute, 1973

A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus m... more A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus musculus) which had a high incidence of naturally occurring lymphoma and elevated indigenous type-C virus activity. Experimental transmission evidence indicated that both the neurologic and lymphomatous disorders almost certainly were caused by the indigenous type-C virus. The virus appeared to have a direct neurotropic effect on anterior horn neurons in the lower spinal cord.

Research paper thumbnail of The epidemiology and virology of C-type virus-associated hematological cancers and related diseases in wild mice

Cancer research, 1976

In several different populations of wild mice, observed over a 35-month period in laboratory geri... more In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies.

Research paper thumbnail of Dietary fat affects immune response, production of antiviral factors, and immune complex disease in NZB/NZW mice

Proceedings of the National Academy of Sciences, 1982

Autoimmune-prone (NZB x NZW)F1 (B/W) mice fed three nearly isocaloric diets with varied fat conte... more Autoimmune-prone (NZB x NZW)F1 (B/W) mice fed three nearly isocaloric diets with varied fat content showed a marked difference in their spontaneous development of immune complex disease and their immune response. Those animals received the diets high in either unsaturated or saturated fats had more severe immune complex nephritis and died earlier than mice on the low-fat diet. Endogenous production of the mouse xenotropic virus was unaffected by dietary fats, but the serum lipoproteins associated with antiviral activity were increased to levels as high as 1:600,000 in the B/W mice on the high-fat diets. These lipoproteins may be partially responsible for the decreased mitogenic response of spleen cells from mice fed the two high-fat diets. The mice receiving a diet high in saturated fats produced substantially higher titers of natural thymocytotoxic autoantibody, an IgM class of antibody, than did the mice maintained either on the high-unsaturated-fat or low-fat diet. In contrast, t...

Research paper thumbnail of Induction of Simian AIDS in Infant Rhesus Macaques Infected with CCR5- or CXCR4-Utilizing Simian-Human Immunodeficiency Viruses Is Associated with Distinct Lesions of the Thymus

Journal of Virology, 2004

ABSTRACTNewborn rhesus macaques were infected with two chimeric simian-human immunodeficiency vir... more ABSTRACTNewborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1)envgenes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIVSF162P3or the CXCR4-utilizing SHIVSF33Aresulted in clinical manifestations consistent with simian AIDS. Most prominent in this study was the detection of severe thymic involution in all SHIVSF33A-infected infants, which is very similar to HIV-1-induced thymic dysfunction in children who exhibit a rapid pattern of disease progression. In contrast, SHIVSF162P3induced only a minor disruption in thymic morphology. Consistent with the distribution of the coreceptors CXCR4 and CCR5 within the thymus, the expression of SHIVSF162P3was restricted to the thymic medulla, whereas SHIVSF33Awas preferentially detected in the cortex. This dichotomy of tissue tropism is similar to the differential tropism of HIV-1 isolates observed in the...

Research paper thumbnail of Akvr-1, a dominant murine leukemia virus restriction gene, is polymorphic in leukemia-prone wild mice

Proceedings of the National Academy of Sciences, 1980

We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two al... more We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two alleles, Akvr-1R (restrictive) and Akvr-1r (susceptible), in a feral population of mice (Mus) musculus domesticus) at a squab farm near Lake Casitas (LC) in southern California. Akvr-1k is a dominant allele that exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-mediated lymphoma in LC (Akvr-1RR) X AKR F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in backcrosses to AKR mice. Akvr-1R likewise is effective in restriction of NB-tropic Moloney murine leukemia virus-induced viremia and NB-tropic Friend virus-induced splenomegaly but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three ecotropic viruses are similar to each other and distinct ...

Research paper thumbnail of Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

Journal of Virology, May 1, 1990

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-ligh... more Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenge exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

Research paper thumbnail of HTLV-III Antibody Screening of Blood Bank Donors

Research paper thumbnail of Experimental vaccine protection against homologous and heterologous strains of feline immunodeficiency virus

Journal of Virology, 1993

More than 90% of cats immunized with inactivated whole infected-cell or cell-free feline immunode... more More than 90% of cats immunized with inactivated whole infected-cell or cell-free feline immunodeficiency virus (FIV) vaccines were protected against intraperitoneal infection with 10 50% animal infectious doses of either homologous FIV Petaluma (28 of 30 cats) or heterologous FIV Dixon strain (27 of 28 cats). All 15 control cats were readily infected with either strain of FIV. Protection appears to correlate with antiviral envelope antibody levels by a mechanism yet to be determined.

Research paper thumbnail of Simian Retroviruses

AIDS and Other Manifestations of HIV Infection, 2004

Animal retroviruses are classified within seven different genera, of which members of five genera... more Animal retroviruses are classified within seven different genera, of which members of five genera are present in primates C-type virus, D-type virus, human T-cell leukemia virus (HTLV), simian T-cell lymphotropic virus (STLV), bovine leukemia virus (BLV), lentiviruses, and spuma or foamy viruses. This chapter reviews the salient biology of each of these five viral groups. Emphasis is placed on the D-type simian retroviruses (SRVs) and lentiviruses (SIVs) because of their etiologic association with simian AIDS (SAIDS). Humans also harbor retroviruses: two strains of human T-lymphotropic virus (HTLV-1 and HTLV-2) with simian counterparts (STLV-1 and STLV-2) and two major strains of lentivirus, human immunodeficiency virus (HIV-1 and HIV-2), which also have simian counterparts (SIVs). In the natural African simian hosts, SIV does not cause any disease, but experimental infection of captive macaques with certain SIV strains, especially from the sooty mangabey, produces a progressive and fatal immunodeficiency syndrome similar to AIDS in humans, making this primate lentivirus model very useful for research into AIDS pathogenesis, vaccines, and antiviral therapy.

Research paper thumbnail of Rhesus Macaques Inoculated With Molecularly Cloned Simian Immunodeficiency Virus

Journal of Medical Primatology, Jun 1, 1989

We have isolated a biologically active molecular clone of simian immunodeficiency virus (SIV), SI... more We have isolated a biologically active molecular clone of simian immunodeficiency virus (SIV), SIVmac 1A11, originally obtained from a rhesus macaque at the New England Regional Primate Research Center. Virus derived from cells transfected with this clone is cytopathic for rhesus peripheral blood mononuclear cells, replicates in cultures of rhesus macrophages, and infects rhesus macaques when inoculated intravenously. Six macaques inoculated with SIVmac 1A11 all became infected and produced antibodies to viral envelope glycoproteins that neutralized virus. Antibodies to viral core proteins were detected in only one animal. No clinical signs of disease were observed throughout 7 months postinoculation.

Research paper thumbnail of Development of a mouse mammary tumor virus-negative mouse strain: a new system for the study of mammary carcinogenesis

Journal of Virology, 1982

All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA in... more All inbred strains of mice transmit one or more copies of mouse mammary tumor virus (MMTV) DNA integrated as proviral sequences. This complicates efforts to define viral-induced mammary carcinogenesis. Here we report the use of surgical nonlethal splenectomy in tissue typing mice and the development of an MMTV-negative mouse strain. The MMTV-negative strain allows study of the involvement of non-MMTV genes in mammary carcinogenesis. In addition, it can be used as a sterile background into which MMTV variants can be introduced. Through the techniques described here, mice containing single MMTV loci or specific combinations can be specially chosen and rapidly developed. In this manner, the oncogenecity of particular MMTV variants may be assessed.