Cytokines and chemokines involved in the defense reaction against HIV-1 and hepatitis B virus: isn't it time to use a standardized nomenclature of the involved mediators?

Discovery of new mediators of immune cell activation and interaction facilitated elucidation of the various ways of defense against infectious agents and happened some 40 years ago. Each involved group of researchers named the mediators according to their scope of investigation; often the same molecules were published at the same time with different names. To avoid confusion resulting from using different names for the same mediators and to prevent a Babylonian confusion, standardization was implemented-as in the field of metrics, music, or science including virology. For cytokines and chemokines a standard nomenclature was proposed some 10 years ago and in conclusion it should be used. In this paper the most relevant biomarkers in HIV-1 and HBV infection and their contribution during viral pathogenesis are listed.

Aspects on the history of transmission and favor of distribution of viruses by iatrogenic action: perhaps an example of a paradigm of the worldwide spread of HIV.

Transmission of infectious agents might be associated with iatrogenic actions of charitable help in health care. An example is the vaccination against yellow fever in USA that transmitted hepatitis B virus. Another example is injections of praziquantel for treatment and cure of schistosomiasis in Central and Northern Africa, with a focus in Egypt that has spread hepatitis C virus. There is no indication that human T-lymphotropic virus type 1 was spread by injection treatment for African trypanosomiasis, syphilis and treponematosis, but these treatments might have contributed to the early spread of human immunodeficiency virus type 1 (HIV-1) in Central Africa. Slave trade contributed as well to the spread of viruses from Africa to the Americas; it was stopped in 1850. Until that date HIV-1 was not transported to the Americas. By analysis of nucleic acid sequence data it can be concluded that the continental spread of HCV and HIV-1 might have started around 1920 with an exponential phase from 1940 to 1970. Further iatrogenic actions that promoted the spread of HCV and HIV-1 might be vaccinations to prevent deadly diseases. The successful vaccination was followed by diminution of the infectious agent in the population such as small pox, yellow fever and measles. Measurements to reduce the spread of plague and cholera were further benefits increasing survival of diseased subjects in a population. Thus, the reduction of exposure to deadly infectious agents might have given a chance to HIV-1 infected subjects to survive and for HIV-1 to be distributed around the world starting from Central Africa in the 1950s.

Effect of antiretroviral HIV therapy on hepatitis B virus replication and pathogenicity.

Coinfections with hepatitis B virus (HBV) and HIV are very frequent. Although HBV is a DNA virus, it replicates via reverse transcription like HIV. Structural similarities between the enzymatic pocket of the HBV DNA polymerase and HIV-1 reverse transcriptase are the basis that certain drugs inhibit both enzymes and thus the replication of both viruses. HBV components increase the pathogenic action of HIV and vice versa directly by certain proteins like HBsAg in the case of HBV and HIV-encoded Tat and Vpr and by disturbing the cytokine balance in affected cells. Antiretroviral therapy is highly beneficial for HIV/HBV-coinfected patients, but carries the risk of drug-induced resistance development and hepatotoxicity. Even with restoration of the immune capacity, signs of hepatic inflammation may develop even after 10 years of treatment.

Regional spread of HIV-1 M subtype B in middle-aged patients by random env-C2V4 region sequencing.

A transmission cluster of HIV-1 M:B was identified in 11 patients with a median age of 52 (range 26-65) in North-East Germany by C2V4 region sequencing of the env gene of HIV-1, who-except of one-were not aware of any risky behaviour. The 10 male and 1 female patients deteriorated immunologically, according to their information made available, within 4 years after a putative HIV acquisition. Nucleic acid sequence analysis showed a R5 virus in all patients and in 7 of 11 a crown motif of the V3 loop, GPGSALFTT, which is found rarely. Analysis of formation of this cluster showed that there is still a huge discrepancy between awareness and behaviour regarding HIV transmission in middle-aged patients, and that a local outbreak can be detected by nucleic acid analysis of the hypervariable env region.

HIV type 2 intergroup recombinant identified in Cameroon.

A unique HIV-2 intergroup recombinant strain was identified in Cameroon. The virus, CM-03-510-03, was amplified from blood collected from a 47-year-old female patient in Douala, Cameroon in 2003 who was seroreactive for HIV-2. A near full-length genome 9089 nucleotides in length was amplified from proviral DNA. The genome for CM-03-510-03 is composed of segments of HIV-2 groups A and B with four recombination break-points and has open reading frames for all the structural and regulatory genes. A comparison of CM-03-510-03 to the only previously reported HIV-2 intergroup recombinant shows that the two strains share one recombination breakpoint but are otherwise distinct from each other. Similar to HIV-1, HIV-2 intergroup recombination is an indication that coinfection with more than one strain has occurred in individuals and is a mechanism that increases strain genetic diversity.

Identification of HIV type 1 group N infections in a husband and wife in Cameroon: viral genome sequences provide evidence for horizontal transmission.

HIV-1 is classified into three groups, M (major), N (non-M non-O), and O (outlier); each group arose from a separate transmission of SIVcpz into humans. HIV-1 group N was recently discovered and infections with this virus are rare with only eight documented cases. All group N infections have been found in Cameroon and there is no evidence of direct linkage between the infected patients. We report here the identification of HIV-1 group N infections in a husband and wife. The group N infection in the husband, 1131-03, was identified first based on seroreactivity in peptide EIAs and confirmed by PCR amplification of group N viral sequences. Subsequently the wife, 1015-04, was evaluated and confirmed to also be infected with a group N virus. Near full-length viral genomes were amplified and sequenced from each patient's specimen. The low level of diversity between the two viral sequences provides evidence of horizontal transmission of group N from one spouse to the other. Patient 1131-03 was receiving antiviral therapy consisting of reverse transcriptase inhibitors; the treatment appears effective for suppression of group N viral replication based on apparently low viral load in plasma specimens collected from the patient and the absence of drug resistance mutations in RT sequences amplified from 1131-03. This report brings to 10 the number of group N infections identified and to 5 the number of group N genomes sequenced. Although group N infections continue to be rare, group N is a pathogenic virus and its prevalence needs to be monitored.

Evaluation of HIV type 1 group O isolates: identification of five phylogenetic clusters.

HIV-1 group O strains have a level of genetic diversity similar to that of strains in group M; however, group O has not been readily classified into genetic subtypes. Phylogenetic classification of group O has been hindered by the limited sequence information available. To facilitate phylogenetic analysis, we sequenced the gag p24 (693 nt), pol p32 (864 nt), and env gp160 (approximately 2700 nt) genes from 39 group O-infected specimens. These specimens include 32 plasma samples collected in Cameroon between 1996 and 1999, 2 specimens collected in the United States, and 5 infections previously isolated in Equatorial Guinea. Phylogenetic analysis of HIV-1 group O sequences resulted in the identification of five clusters that are maintained across gag, pol, and env, generally supported by high bootstrap values, and approximately equidistant from each other. In addition to the group O clusters, several isolates branch independently and are equidistant from the other group O isolates. Cluster I comprises greater than 50% of the group O isolates and is a diverse set of isolates that is subdivided into subclusters. The average intra-, sub-, and intercluster distances for group O are similar to the corresponding distances for group M subtypes. The five group O clusters have characteristics similar to those of group M subtypes. Thus the data presented may form the basis for classification of group O into subtypes. However, full-length genomes representing each group O cluster will be required to formalize a group O subtype classification.

Near full-length genomes of 15 HIV type 1 group O isolates.

Human immunodeficiency virus type 1 (HIV-1) is classified into three distinct groups; M (major), N (non-M/non-O), and O (outlier). Group M strains are further subclassified into subtypes, subsubtypes, and circulating recombinant forms (CRF). While the level of genetic diversity within group O is similar to that between group M subtypes, group O has not been classified into subtypes. A previous study, based on the phylogenetic analyses of the gag p24, pol p32, and env gp160 sequences from 39 group O isolates, laid the foundation for the classification of group O subtypes. Five phylogenetic clusters, I-V, were identified that have characteristics analogous to group M subtypes. However, a complete phylogenetic analysis and classification of group O requires the availability of at least two full-length and one partial genomes for each group O phylogenetic cluster. In this study, 15 group O isolates were selected for full genome sequencing. Phylogenetic analysis of the 15 sequences with eight additional group O genomes supports the classification of three group O subtypes (I-III) and the potential existence of one CRF (IV) and at least one additional subtype (V). The group O subtypes are equidistant to each other and lack subsegments of other subtypes. The intra- and intersubtype genetic distances for group O are similar in magnitude to the corresponding distances for group M subtypes. Intersubtype recombination was identified in three of the 23 (13%) group O genomes. Formal classification of group O subtypes should be forthcoming pending the analysis of additional group O genomes and agreement of the HIV nomenclature committee.

Near full-length sequence of HIV type 1 subtype J strain 04CMU11421 from Cameroon.

Although Cameroon, in west central Africa, has a relatively low HIV prevalence of 5-6%, all HIV-1 groups (M, N, O, and P), nearly all HIV-1 group M subtypes, and numerous intersubtype recombinant forms have been identified in Cameroon. In this report, we describe the near full-length sequence of 04CMU11421, an HIV-1 group M subtype J strain collected in Cameroon in 2004. Phylogenetic analysis of the genome sequence shows high bootstrap support with three subtype J reference sequences in the HIV Sequence database. Therefore, 04CMU11421 represents a fourth pure subtype J isolate and the first reported in Cameroon.

Four new HIV-1 group N isolates from Cameroon: Prevalence continues to be low.

Analysis of 3555 HIV-seropositive specimens, collected in Cameroon from 2002 to 2006, led to the identification of four HIV-1 group N infections based on differential seroreactivity to HIV env-derived peptides and proteins and confirmation by nucleic acid amplification. Group N prevalence continues to be low accounting for only 0.1% of HIV infections in Cameroon. Near full-length genomic sequences were obtained from viral RNA or proviral DNA by PCR amplification of overlapping fragments for three isolates, 06CM-U14296, 06CM-U14842, and 02CM-SJGddd. Two genome segments, partial pol and env-nef, were obtained from viral RNA for the fourth isolate, 02CM-TIM0217. With the four group N isolates identified in this study and group N sequences previously reported, eight near full-length and five partial genome sequences are now available. Despite genetic divergence from HIV-1 group M and O, all of the group N infections evaluated by five commercial HIV immunoassays were detected.

HIV type 1 group M subtype G in Cameroon: five genome sequences.

Near full-length viral genome sequences were obtained for five putative subtype G candidates identified in HIV-infected Cameroonian blood donors, based on partial genome sequences for the gag, pol, and env regions. Phylogenetic analysis of the genome sequences shows that all five strains are pure subtype G with no indication of intersubtype recombination. The Cameroon subtype G sequences did not form a geographically based subcluster and were intermixed within the subtype G branch with isolates from several different countries. HIV-1 group M subtype G accounts for only 4.5% of HIV infections in Cameroon. However, genome segments of subtype G are present in 67% of all infections and 80% of infections due to intersubtype recombinant strains in Cameroon. The addition of five subtype G genome sequences to the HIV database may contribute to a better understanding of the origins and classification of HIV-1 subtypes and CRFs.

The prevalence of diverse HIV-1 strains was stable in Cameroonian blood donors from 1996 to 2004.

OBJECTIVE: The HIV epidemic in Cameroon is characterized by a high level of strain diversity despite a relatively low prevalence of infection. In this study, HIV strains infecting blood donors in Cameroon were characterized to determine the prevalence of subtypes and intersubtype recombinants and if strain prevalence was changing over time. METHODS: From 1996 through 2004, 676 HIV-infected blood donations were collected at blood banks in Douala and Yaoundé, Cameroon. A subset of the HIV-1 group M strains (n = 574) were classified based on phylogenetic analysis of viral sequences from the gag p24, pol integrase, and env gp41 regions. RESULTS: HIV-1 group M accounted for 97.3% (n = 658) of infections, whereas group O was present in 2.2% (n = 15) and HIV-2 in 0.4% (n = 3). Within the group M infections, 14 subtypes and circulating recombinant forms (CRFs) and unique recombinant forms (URFs) were identified. Overall, CRFO2_AG accounted for 58.2% of infections, URFs 14.8%, and levels of subtypes, A, B, C, D, F2, and G, and CRFs, 01, 06, 09, 11, 13, 22, and 37, varied from 0.2% to 6.1%. Evaluation of HIV strains present in the donor population over this 9-year period showed no substantial changes in the proportion of infections caused by each subtype and CRF, the percentage of intersubtype recombinants, or the strain composition of the URFs. CONCLUSIONS: HIV-1 strain diversity in Cameroon did not significantly change, suggesting a mature and relatively stable epidemic.

No evidence for simian virus 40 DNA sequences in malignant non-Hodgkin lymphomas.

DNA sequences coding for simian virus 40 (SV40) large T antigen have been detected at different frequencies in human non-Hodgkin's lymphomas (NHL) by PCR techniques as well as immunohistochemistry. A highly sensitive quantitative real-time PCR specific for a sequence of SV40 large T antigen was established to test whether SV40 DNA is present in malignant lymphomas of German patients. Thirty-three lymph node samples obtained from 27 patients with NHL and 6 patients with Hodgkin's disease (HD) were tested in addition to 48 samples of peripheral blood mononuclear cells (PBMNC) from patients with NHL containing between 0.1% and >90% circulating lymphoma cells determined by PCR. Fourteen lymph nodes obtained from patients with other diseases than malignant lymphomas and 47 PBMNC samples from healthy volunteers served as controls. All samples from patients with malignant lymphomas and all controls were negative for SV40 DNA by quantitative real-time. In contrast, EBV-DNA could be detected in 29 of 46 DNA preparations isolated from lymph nodes (63%) and in 20 of 47 DNA preparations from PBMNC. EBV-positive samples contained between 5 and 80,000 EBV copies per 100,000 cells. Our results do not support the hypothesis that SV40 plays a major role in the etiology of malignant lymphomas and, in addition, they exclude a clonal SV 40 infection of malignant lymphoma cells in all samples investigated.